Measuring an analyte in breath using a porous structure containing a reactant

ABSTRACT

Various devices are disclosed for measuring the concentration of an analyte, such as acetone, in a breath sample. The disclosed devices include a disposable cartridge containing a reactive material that extracts the analyte from a breath sample passed through the cartridge. In some embodiments, the cartridge contains a solid, porous structure (such as a disk, bowl or puck) that contains the reactive material. To induce a chemical reaction for measuring the quantity of the extracted analyte, the porous structure may be brought into contact with a sponge or pad that dispenses developer solution to the porous structure. Also disclosed are devices for routing a breath sample through the cartridge during exhalation, and for analyzing a reaction in the cartridge to measure a concentration of the analyte.

PRIORITY CLAIM

This application claims the benefit of U.S. Provisional Patent Appl. No.62/675,109, filed May 22, 2018, the disclosure of which is herebyincorporated herein by reference.

BACKGROUND Field

The present disclosure relates to apparatuses, systems, and methods forsensing or measuring chemical components or constituents (e.g.,analytes) in the breath of a patient or “subject,” and preferablyendogenous analytes in breath, and correspondingly, to devices andmethods for regulating the flow of the breath sample during thepre-measurement capture process and/or during such sensing ormeasurement.

Description of the Related Art

The importance or benefits of measuring the presence or concentration ofchemical constituents in the body to aid in assessing a patient orsubject's physiological or pathophysiological state is well known in themedical and diagnostic communities. Standard approaches tochemically-based diagnostic screening and analysis typically involveblood tests and urine tests.

Blood tests of course require that blood be drawn. Patients associatethis procedure with pain, a factor that can have adverse implicationsfor patient compliance in home-based assessments. In clinical settings,the need to draw blood typically requires trained personnel to draw theblood, carefully and properly label it, handle it and the like. It istypically necessary to transport the sample to a laboratory, often offsite, for analysis. Given the logistics and economics, the lab analysisusually is carried out in bulk on large numbers of samples, thusrequiring bulk handling and logistics considerations and introducingdelay into the time required to obtain results. It is then typicallynecessary for follow-up analysis by the physician or clinician to assessthe lab results and further communicate with the patient. In large partbecause of these logistics and delays, it is usually necessary for thepatient or subject to return for a follow up visit, thus takingadditional clinical time and causing additional expense.

Urine tests involve similar drawbacks. Such tests can be messy,unsanitary, and introduce issues with respect to labeling, handling andcontamination avoidance. They also usually involve lab analysis, withassociated delays and expense. As with blood, urine tests, it istypically necessary to transport the samples to an off-site laboratoryfor analysis. Given the logistics, the lab analysis usually is carriedout in bulk on large numbers of samples, thus again involving delay andexpense.

There are many instances in which it is desirable to sense the presenceand/or quantity or concentration of an analyte in a gas. “Analyte” asthe term is used herein is used broadly to mean the chemical componentor constituent that is sought to be sensed using devices and methodsaccording to various aspects of the invention. An analyte may be orcomprise an element, compound or other molecule, an ion or molecularfragment, or other substance that may be contained within a fluid. Insome instances, embodiments and methods, there may be more than oneanalyte present, and an objective is to sense multiple analytes. “Gas”as the term is used herein also is used broadly and according to itscommon meaning to include not only pure gas phases but also vapors,non-liquid fluid phases, gaseous colloidal suspensions, solid phaseparticulate matter or liquid phase droplets entrained or suspended ingases or vapors, and the like. “Sense” and “sensing” as the terms areused herein are used broadly to mean detecting the presence of one ormore analytes, or to measure the amount or concentration of the one ormore analytes.

The use of breath as a source of chemical analysis can overcome many ofthese drawbacks. The presence of these analytes in breath and theirassociated correlations with physiological or pathophysiological statesoffer the substantial theoretical or potential benefit of providinginformation about the underlying or correlated physiological orpathophysiological state of the subject, in some cases enabling one toscreen, diagnose and/or treat a patient or subject easily and costeffectively. Breath analysis can avoid painful invasive techniques suchas with blood tests, and messy and cumbersome techniques such as urineanalysis. Moreover, in many applications test results can be obtainedpromptly, e.g., during a single typical patient exam or office visit,and cost effectively.

As is well known in the field of pulmonology, breath, and particularlybreath exhalations, comprise a range of chemical components, oranalytes. An “analyte” is a chemical component or constituent that is acandidate for sensing, detection or measurement. Breath compositionvaries somewhat from subject to subject, and within a given subject,from time to time, depending on such factors as physical condition(e.g., weight, body composition), diet (e.g., general diet, recentintake of food, liquids, etc.), exertion level (e.g., resting metabolicrate versus under stress or exercise), and pathology (e.g., diseasedstate). Approximately 200 to 300 analytes can be found in human breath.

Certain breath analytes have been correlated with specific physiologicalor pathophysiological states. Such correlations are particularly usefulfor “endogenous” analytes (i.e., those that are produced by the body),as opposed to “exogenous” analytes (i.e., those that are present inbreath strictly as a result of inhalation, ingestion or consumption andsubsequent exhalation by the subject). Examples are set forth in Table1.

TABLE 1 Candidate Analyte Illustrative Pathophysiology/Physical StateAcetone Lipid metabolism (e.g., epilepsy management, nutritionalmonitoring, weight loss therapy, early warning of diabeticketoacidosis), environmental monitoring, acetone toxicity, congestiveheart failure, malnutrition, exercise, management of eating disordersEthanol Alcohol toxicity, bacterial growth Acetaldehyde Ammonia Liver orrenal failure, protein metabolism, dialysis monitoring, early detectionof chronic kidney disease, acute kidney disease detection and managementOxygen and Carbon Resting metabolic rate, respiratory quotient, Dioxideoxygen uptake Isoprene Lung injury, cholesterol synthesis, smokingdamage Pentane Lipid peroxidation (breast cancer, transplant rejection),oxidative tissue damage, asthma, smoking damage, chronic obstructivepulmonary disease (“COPD”) Ethane Smoking damage, lipid peroxidation,asthma, COPD Alkanes Lung disease, cancer metabolic markers BenzeneCancer metabolic monitors Carbon-13 H. pylon infection MethanolIngestion, bacterial flora Leukotrienes Present in breath condensate,cancer markers Hydrogen peroxide Present in breath condensateIsoprostane Present in breath condensate, cancer markers PeroxynitritePresent in breath condensate Cytokines Present in breath condensateGlycans Glucose measurement, metabolic anomalies (e.g., collected fromcellular debris) Carbon monoxide Inflammation in airway (asthma,bronchiectasis), lung disease Chloroform Dichlorobenzene Compromisedpulmonary function Trimethyl amine Uremia Dimethyl amine Uremia Diethylamine Intestinal bacteria Methanethiol Intestinal bacteriaMethylethylketone Lipid metabolism O-toluidine Cancer marker Pentanesulfides Lipid peroxidation Hydrogen sulfide Dental disease, ovulationSulfated hydrocarbon Cirrhosis Cannabis Drug concentration G-HBA Drugtesting Nitric oxide Inflammation, lung disease Propane Proteinoxidation, lung disease Butane Protein oxidation, lung disease OtherKetones (other Lipid metabolism than acetone) Ethyl mercaptane CirrhosisDimethyl sulfide Cirrhosis Dimethyl disulfide Cirrhosis Carbon disulfideSchizophrenia 3-heptanone Propionic acidaemia 7-methyl tridecane Lungcancer Nonane Breast cancer 5-methyl tridecane Breast cancer 3-methylundecane Breast cancer 6-methyl pentadecane Breast cancer 3-methylpropanone Breast cancer 3-methyl nonadecane Breast cancer 4-methyldodecane Breast cancer 2-methyl octane Breast cancer Trichloroethane2-butanone Ethyl benzene Xylene (M, P, O) Styrene TetrachloroetheneToluene Ethylene Hydrogen

The inherent relative advantage of breath analysis over othertechniques, together with the relatively wide array of analytes andanalyte correlations, illustrate that the potential benefits breathanalysis offers are substantial.

Notwithstanding these potential benefits, however, with the exception ofbreath ethanol devices used for law enforcement, there has been apaucity of breath analyzers on the commercial market, particularly inmedically-related applications. This lack of commercialization isattributable in large measure to the relatively substantial technicaland practical challenges associated with the technology. Principal amongthem is the requirement for sensitivity. Analytes of interest,particularly endogenous analytes, often are present in extremely lowconcentrations, e.g., of only parts per million (“ppm”) or parts perbillion (“ppb”). In addition, the requirements for discrimination orselectivity is of critical concern. As noted herein above, breathtypically includes a large number, sometimes hundreds, of chemicalcomponents in a complex matrix. Breath also usually has considerablemoisture content. Chemical sensing regimes conducive for breath ammoniameasurement, for example, are preferably sensitive to 50 ppb in thepresence of 3 to 6% water vapor with 3 to 5% carbon dioxide.Successfully and reliably sensing a particular analyte in such aheterogeneous and chemically-reactive environment presents substantialchallenges.

Most publicly-known breath analysis devices and methods involve using asingle breath, and more specifically a single exhalation, as the breathsample to identify or measure a single analyte. The sample is collectedand analyzed to determine whether the analyte is present, and in somecases, to measure its concentration. The breath analysis systemintroduced by Abbott Laboratories, e.g., in U.S. Pat. Nos. 4,970,172,5,071,769, and 5,174,959, provides an illustrative example. There,Abbott used a single exhalation from a patient to detect the presence ofacetone to obtain information about fat metabolism.

Notwithstanding the potential benefits of breath analysis, particularlyportable breath analysis devices for home or field use, commercialofferings of such devices have been available only recently, and theaccuracy and reliability in such settings have left much room forimprovement. Practical breath analysis devices must operate accuratelyand reliably in the context of their use, e.g., in patient homes,clinics, etc., in varying environments, (temperatures, humidity, etc.),with various types of patients, over the life of the devices.

The use of multiple breaths is substantially lesser known and studied.Published reports generally have been limited to the determination ofthe production rate of carbon dioxide and the consumption rate ofoxygen. This technique was developed due to the presence of these twoanalytes (oxygen and carbon dioxide) in the ambient atmosphere.

These approaches have been limited and relatively deficient, however,for example, in that the breath sample or samples are collected in bulk,so that the analyte of interest is mixed in with other constituents.This often dilutes the analyte and increases the difficulty ofdiscriminating the desired analyte. These approaches also limit theflexibility of the breath analysis to undertake more specialized orcomplex analyses.

Additionally, such approaches are relatively deficient because theinstrumentation used for single breath analysis usually is differentfrom and sometimes inadequate for multiple breath analyte measurement.

Yet another challenge to breath analysis involves the fluid mechanicalproperties of the breath sample as it travels through the measurementdevice.

There is considerable advantage in providing breath analysis devicesthat can accurately and reliably sense or measure breath analytes in aclinical or patient home setting. Thus, there is a need for small orportable, cost effective devices and components.

In many instances, there is a need or it is desirable to make theanalysis for an analyte in the field, or otherwise to make suchassessment without a requirement for expensive and cumbersome supportequipment such as would be available in a hospital, laboratory or testfacility. It is often desirable to do so in some cases with a largelyself-contained device, preferably portable, and often preferably easy touse. It also is necessary or desirable in some instances to have thecapability to sense the analyte in the fluid stream in real time or nearreal time. In addition, and as a general matter, it is highly desirableto accomplish such sensing accurately and reliably.

The background matrix of breath presents numerous challenges to sensingsystems, which necessitate complex processing steps and which furtherpreclude system integration into a form factor suitable for portableusage by layman end-users. For example, breath contains high levels ofhumidity and moisture, which may interfere with the sensor or causecondensation within the portable device, amongst other concerns. Also,the flow rate or pressure of breath as it is collected from a usertypically varies quite considerably. Flow rate variations are known toimpact, often significantly, the response of chemical sensors. Breath,especially when directly collected from a user, is typically at or nearcore body temperature, which may be considerably different than theambient temperature. Additionally, body temperature may vary from userto user or from day to day, even for a single user. Devising a breathanalyzer thus is a non-trivial task, made all the more difficult toextent one tries to design and portable and field-amenable device.

Notably, the measurement of endogenous analytes in breath presentsdifferent challenges and requires different techniques and devices thanthe measurement of exogenous analytes. Endogenous analytes are thosethat are produced by the body, excluding the lumen of thegastrointestinal tract, whereas exogenous analytes are those that arepresent in breath as a result of the outside influence or as a result ofuser consumption. However, many analytes are produced endogenously andcan also be exogenously introduced. For example, ammonia is producedendogenously through the metabolism of amino acids, but can also beintroduced exogenously from the environment such as ammonia-containinghousehold cleaning supplies. The term “endogenous” is used according toits common meaning within the field. Endogenous analytes are produced bynatural or unnatural means within the human body, its tissues or organs,typically excluding the lumen of the gastrointestinal tract.

There are a number of significant challenges to measuring endogenousanalytes in breath. Endogenous analytes typically have significantlylower concentrations in the breath, often on the order of parts permillion (“ppm”), parts per billion (“ppb”), or less. Additionally,measurement of endogenous analytes requires discrimination of theanalyte in a complex matrix of background gases. Instead of typicalatmospheric gas composition (e.g., primarily nitrogen), exhaled breathhas high humidity content and larger carbon dioxide concentration. Thisleads to unique challenges in chemical sensitivity, selectivity andstability. For example, chemistries conducive for breath ammoniameasurement are preferably sensitive to 50 ppb in the presence of 3 to6% water vapor with 3 to 5% carbon dioxide.

Because of the historical difficulty in even detecting endogenous breathanalytes, other challenges have not been extensively investigated.Examples of such challenges include: (a) correlating the analytes tohealth or disease states, (b) measuring these analytes givencharacteristics of human exhalation, e.g., flow rate and expiratorypressure, (c) measuring these analytes sensitively and selectively, and(d) doing all these in a portable, cost effective package that can beimplemented in medical or home settings.

Colorimetric devices are one method for measuring a reaction involving abreath analyte. Colorimetric approaches to endogenous breath analysishave historically been plagued with lengthy response times, andexpensive components. Often such analysis has to be performed in alaboratory. Thus there remains a need for a breath analyzer that canmeasure endogenous breath components present in relatively lowconcentrations, such as acetone, accurately and quickly, without a longwait period for results, in addition to being inexpensive and useable bythe layperson. It is also preferable if the breath analyzer is capableof measuring multiple analytes.

The above-noted problems are not necessarily addressed by all of thedisclosed embodiments. For example, some problems may be addressed bysome embodiments, while other problems are addressed by otherembodiments. Thus, the foregoing description should not be relied uponto limit the scope of protection.

BRIEF DESCRIPTION OF THE DRAWINGS

FIGS. 1A-1D show various views of an embodiment of a sample capturecartridge. FIG. 1A shows a side view of an embodiment of a samplecapture cartridge. FIG. 1B shows a top view of the sample capturecartridge of FIG. 1A. FIG. 1C shows a cut-away view of a side view ofthe sample capture cartridge of FIG. 1A. FIG. 1D shows a bottom view ofan embodiment of the sample capture cartridge of FIG. 1A.

FIGS. 2A-2B show exploded views of an embodiment of a sample capturecartridge.

FIG. 3 shows a bottom-biased three-quarter view of an embodiment of asample capture cartridge and an air flow path there through.

FIGS. 4A-4J show various view of an embodiment of a cartridge lens cap.FIG. 4A shows a top-biased three-quarter view of an embodiment of acartridge lens cap. FIG. 4B shows a bottom-biased three-quarter view ofan embodiment of a cartridge lens cap. FIG. 4C shows a bottom-biasedthree-quarter view of another embodiment of a cartridge lens cap. FIG.4D shows a top view of the cartridge lens cap of FIG. 4A. FIG. 4E showsa side view of the cartridge lens cap of FIG. 4A. FIG. 4F shows acut-away view of the cartridge lens cap of FIG. 4E. FIG. 4G shows abottom view of the cartridge lens cap of FIG. 4A. FIG. 4H shows acartridge lens cap having an upper portion and a lower portion, theupper and lower portions being decoupled from each other. FIG. 4I showsthe cartridge lens cap of FIG. 4H having the upper and lower portionsbeing coupled together. FIG. 4J shows the cartridge lens cap of FIGS.4H-4I with a porous bowl held between the two portions.

FIGS. 5A-5F show various views of an embodiment of a bowl. FIG. 5A showsa side view of an embodiment of a porous bowl. FIG. 5B shows a cut awayview of a side view of the porous bowl of FIG. 5A. FIG. 5C shows atop-biased cut-away view of the porous bowl of FIG. 5A. FIG. 5D shows atop-biased cut-away view of another embodiment of a porous bowl. FIG. 5Eshows a top view of the porous bowl of FIG. 5A. FIG. 5F shows a bottomview of the porous bowl of FIG. 5A.

FIGS. 6A-6C show various views of an embodiment of a cartridge desiccantcanister. FIG. 6A shows a top view of an embodiment of a cartridgedesiccant canister. FIG. 6B shows a bottom view of the cartridgedesiccant canister of FIG. 6A. FIG. 6C shows a cut-away view of a sideview of the cartridge desiccant canister of FIG. 6A.

FIG. 7A-7C show various views of an embodiment of a desiccant retainer.FIG. 7A shows a top view of an embodiment of a desiccant retainer. FIG.7B shows a bottom view of the desiccant retainer of FIG. 7A. FIG. 7Cshows a cut-away view of a side view of the desiccant retainer of FIG.7A.

FIGS. 8A-8F show various views of an embodiment a sample collectionwhistle. FIGS. 8A-8B show various views of a sample capture cartridgebeing loaded into an embodiment of a sample collection whistle. FIG. 8Cshows a top view of an embodiment of a sample collection whistle. FIG.8D shows a side view of the sample collection whistle of FIG. 8C. FIG.8E shows a rear view of the sample collection whistle of FIG. 8C. FIG.8F shows a front view of the sample collection whistle of FIG. 8C.

FIGS. 9A-9F show various views of an embodiment of a sample capturecartridge loaded into a sample collection whistle. FIGS. 9A-9B showvarious views of an embodiment of a sample capture cartridge after beingloaded into an embodiment of a sample collection whistle. FIG. 9C showsa top view of an embodiment of a sample capture cartridge loaded into anembodiment of a sample collection whistle. FIG. 9D shows a side view ofthe sample capture cartridge loaded into the sample collection whistleof FIG. 9C. FIG. 9E shows a rear view of the sample capture cartridgeloaded into the sample collection whistle of FIG. 9C. FIG. 9F shows afront view of the sample capture cartridge loaded into the samplecollection whistle of FIG. 9C.

FIGS. 10A-10D show various views of the internal components of thesample collection whistle of FIG. 8C. FIGS. 10A & 10B show a top-biasedthree-quarter view of the internal components of the sample collectionwhistle of FIG. 8C. FIG. 10C shows a rear view of the internalcomponents of the sample collection whistle of FIG. 8C. FIG. 10D shows aside cut-away view of the sample collection whistle of FIG. 8C.

FIGS. 11A-11C show various views of an embodiment of a sample collectionwhistle configured to make sound during use. FIG. 11A shows a top viewof an embodiment of a sample collection whistle configured to make soundduring use. FIG. 11B shows a front view of an embodiment of a samplecollection whistle configured to make sound during use. FIG. 11C showsvarious internal noise making components of the sample collectionwhistle configured to make sound during use of FIG. 11B.

FIGS. 12A-12B show various views in an extended configuration of anembodiment of a one piece breather that may be used to collect samples.

FIG. 12C shows an embodiment of a cartridge sealing grommet that may beused in conjunction with various sample collection devices, such as theone piece breather of FIGS. 12A-12B.

FIGS. 13A-13B show various views in a folded usable configuration of theone piece breather of FIGS. 12A-12B, which may be used to collectsamples. FIG. 13A shows the one piece breather of FIGS. 12A-12B, foldedand ready for use. FIG. 13B shows the one piece breather of FIGS.12A-12B, folded and ready for use and into which an embodiment of asample capture cartridge has been loaded.

FIGS. 14A-14C show various views of breather wing positions of anembodiment of a one piece breather. FIG. 14A shows the one piecebreather of FIG. 13B having breather wings in a relaxed position. FIG.14B shows the one piece breather of FIG. 13B having breather wings in asample collection position. FIG. 14C shows the one piece breather ofFIG. 13B having breather wings in a cartridge ejection position.

FIG. 15A shows an exploded view of an embodiment of a rapid test samplecollection cartridge.

FIG. 15B shows a sample collection frit that may be used in conjunctionwith the rapid test sample collection cartridge of FIG. 15A.

FIGS. 16A-16B show various views of a rapid test sample collectioncartridge.

FIGS. 17A-17B show select steps in an embodiment of a method of using arapid test sample collection cartridge.

FIGS. 18A-18E show various views of an embodiment of a base unit. FIG.18A shows a top-biased front three-quarters view of an embodiment of abase unit. FIG. 18B shows a side view of an embodiment of a base unit.FIG. 18C shows a front view of an embodiment of a base unit. FIG. 18Dshows a top view of an embodiment of a base unit. FIG. 18E shows atop-biased front three-quarters view of an embodiment of a base unithaving a cartridge tray in an extended position.

FIGS. 19A-19C show various view of the internal components of anembodiment of a base unit. FIG. 19A shows a top-biased three-quartersview of the internal components of an embodiment of a base unit. FIG.19B shows a front view of the internal components of an embodiment of abase unit. FIG. 19C shows a side view of the internal components of abase unit.

FIGS. 20A-20C show various views of an embodiment of a dispensingmechanism. FIG. 20A shows a top view of an embodiment of a dispensingmechanism in a relaxed configuration. FIG. 20B shows a top-biasedthree-quarters view of an embodiment of a dispensing mechanism in arelaxed configuration. FIG. 20C shows a front cut-away view of anembodiment of a dispending mechanism in a relaxed configuration.

FIGS. 21A-21C show various views of an embodiment of a dispensingmechanism. FIG. 21A shows a top view of an embodiment of a dispensingmechanism in an actuated configuration. FIG. 20B shows a top-biasedthree-quarters view of an embodiment of a dispensing mechanism in anactuated configuration. FIG. 20C shows a front cut-away view of anembodiment of a dispending mechanism in an actuated configuration.

FIGS. 22A-22C show various views of an embodiment of a drip-resistantdropper tip. FIG. 22A shows a side view of an embodiment of adrip-resistant dropper tip. FIG. 22B shows a top-biased three-quartersview of a drip-resistant dropper tip. FIG. 22C shows a bottom-biasedthree-quarters view of a drip-resistant dropper tip.

FIG. 23A shows a top-biased front three-quarters view of an embodimentof a base unit having a cartridge tray in an extended position. FIG. 23Bshows a side cut-away view of an embodiment of a base unit having acartridge tray in an extended position.

FIGS. 24A-24C show various views of an embodiment of a base unit. FIG.24A shows a front view of an embodiment of a base unit. FIG. 24B shows afront-side view of an embodiment of a base unit. FIG. 24C shows afront-side view of an embodiment of a base unit having a cartridge trayin an extended position.

FIG. 25 shows a system for collecting and analyzing a sample using asample capture cartridge, a sample collection whistle, a base unit, anda mobile phone.

FIGS. 26A-26E show various views of an embodiment of a sample capturecartridge loaded into a sample collection whistle. FIGS. 26A-26B showtop three-quarters view of a sample collection whistle, with FIG. 26Abeing front-biased and FIG. 26B being rear-biased. FIGS. 26C-26E showvarious views of the internal components of the sample collectionwhistle of FIGS. 26A-26B. FIG. 26C shows a front-biased view of theinternal components of the sample collection whistle. FIG. 26D shows theinternal components of the sample collection whistle in aflow-permitting configuration. FIG. 26E shows the internal components ofthe sample collection whistle in a flow-blocking configuration.

FIGS. 27A-27B show an embodiment of a rotary valve that may be used inconnection with various sample collection whistles disclosed herein.FIG. 27A shows the rotary valve in a flow-permitting configuration. FIG.27B shows the rotary valve in a flow-blocking configuration.

FIGS. 28A-28C show various views of an embodiment of a sample collectionwhistle. FIG. 28A shows a sample collection whistle from a front-biasedthree-quarters view. FIG. 28B shows a sample collection whistle from aright side view. FIG. 28C shows a sample collection whistle from a topview.

FIGS. 29A-29C show the sample collection whistle of FIGS. 28-28C with asample capture cartridge loaded into the sample collection whistle. FIG.29A shows a sample capture cartridge loaded into the sample collectionwhistle from a front-biased three-quarters view. FIG. 29B shows a samplecapture cartridge loaded into the sample collection whistle from a rightside view. FIG. 29C shows a sample capture cartridge loaded into thesample collection whistle from a top view.

FIGS. 30A-30C show cross-sectional views of the sample collectionwhistle of FIGS. 28A-28C and 29A-29C. FIG. 30A shows a right sidecross-sectional view of the sample collection whistle of FIG. 28C takenalong line J-J. FIG. 30B shows a right side cross-sectional view of thesample collection whistle of FIG. 29C taken along line K-K.

FIG. 30C shows a right-front biased three-quarters view of the samplecollection whistle of FIG. 29C taken along line L-L.

FIGS. 31A-31E show various views of an embodiment of a base unit. FIG.31A shows a top-right biased three-quarters view of the base unit. FIG.31B shows a front view of the base unit. FIG. 31C shows a rear view ofthe base unit. FIG. 31C shows a right side view of the base unit. FIG.31D shows a left side view of the base unit.

FIGS. 32A-32C show various view of various internal components of a baseunit.

FIGS. 33A-33C show various views of an embodiment of a developer tank.FIG. 33A shows a side view of the developer tank. FIG. 33B shows abottom-biased three-quarters view of the developer tank. FIG. 33C showsa cross-sectional view of the developer tank.

FIGS. 34A-34B show various views of an embodiment of a nozzle. FIG. 34Ashows the nozzle in a closed position. FIG. 34B shows the nozzle in anopen position.

FIGS. 35A-35B show various views of an embodiment of a bleed valve. FIG.35A shows the bleed valve in a closed position. FIG. 35B shows the bleedvalve in an open position.

FIGS. 36A-36B illustrate a process for dispensing developer solutionfrom a fibrous sponge to a porous structure that contains a reactant.

DETAILED DESCRIPTION OF SPECIFIC EMBODIMENTS

Sample Collection Cartridge

FIG. 1A illustrates an embodiment of a sample capture cartridge 100 thatmay be used to collect a fluid sample, e.g., to collect a fluid sampleaccording to any of the number of methods disclosed herein. The samplecapture cartridge 100, as shown in FIG. 1A, includes a cartridge lenscap 110 that has a number of lens cap vents 114 and fits on a cartridgedesiccant canister 140, e.g., fits securely on the cartridge desiccantcanister 140. The sample capture cartridge 100 may have a diameter ofbetween about 5-30 mm, between about 5.5-28 mm, between about 6-26 mm,between about 6.5-24 mm, between about 7-22 mm, between about 7.5-20 mm,between about 8-18 mm, between about 8.5-16 mm, between about 9-14 mm,between about 9.5-12 mm, or any other diameter that advantageouslyfacilitates use and collection of samples as disclosed herein. Thesample capture cartridge 100 may have a combined height, including atleast both the cartridge lens cap 110 and the cartridge desiccantcanister 140, of between about 6-40 mm, between about 7-38 mm, betweenabout 8-36 mm, between about 9-34 mm, between about 10-32 mm, betweenabout 11-30 mm, between about 12-28 mm, between about 13-26 mm, betweenabout 14-24 mm, between about 15-22 mm, between about 16-20 mm, or anyother combined height that facilitates use and collection of samples asdisclosed herein.

FIG. 1B illustrates a top view of the sample capture cartridge 100 ofFIG. 1A, showing the cartridge lens cap 110 surrounded by several, e.g.,eight, lens cap vents 114. Various embodiments of a cartridge lens cap110 are discussed in more detail in connection with FIGS. 4A-4G.

FIG. 1C illustrates a sectional view of the sample capture cartridge 100of FIG. 1A taken along line A-A. Additional detail regarding theinteraction of the various pieces of the sample capture cartridge 100 isprovided herein. Generally, the quantity of silica 120 resides in theinterior of the porous bowl 130. The porous bowl 130 containing thequantity of silica 120 is fit into the cartridge lens cap 110 such thatthe edges of the porous bowl 130 prevent the silica 120 from falling outof the lens cap vents 114 of the cartridge lens cap 110. The cartridgelens cap 110 (already containing the porous bowl 130 containing thesilica 120) is fitted onto the cartridge desiccant canister 140. Thecartridge desiccant canister 140 contains a quantity of desiccant 150held in place, under a ported upper surface, by a cartridge desiccantretainer 160, which also has at least one port. Therefore, the samplecapture cartridge 100 defines a continuous flow path therethrough. Aswill be understood with reference to FIG. 1C and FIG. 3, in at least oneembodiment, the continuous flow path proceeds from the base of thesample capture cartridge 100, into the bottom opening of the cartridgedesiccant canister 140, through the ports of the cartridge desiccantretainer 160, through the desiccant 150 (held between the cartridgedesiccant retainer 160 and the cartridge desiccant canister 140) throughthe ports in the cartridge desiccant canister 140, through the canistercavity 144, through the base of the porous bowl 130, through the silica120, through the sides of the porous bowl 130, and out through the lenscap vents 114. Of course, one of ordinary skill in the art willunderstand that various modifications to this flow path may be made.

FIG. 1D illustrates the sample capture cartridge 100 shown in FIGS. 1Aand 1C from the bottom. The cartridge desiccant canister 140 may beseen, as well as the cartridge desiccant retainer 160 holding in aquantity of desiccant 150. Additionally, a desiccant retainer notch 162may be seen.

The cartridge lens cap 110 is shaped generally like a cylinder andincludes a lens cap window 112 and at least one lens cap vent 114. Insome embodiments, the cartridge lens cap 110 may have shapes other thana cylinder. For example, the cartridge lens cap 110 may be have fourside, five sides, six sides, seven sides eight sides, or any othernumber of sides. Circular cartridge lens caps 110 may advantageouslysimplify the manufacturing process, but one of ordinary skill in the artwill easily understand that a cartridge lens cap 110 having othernumbers of sides may be used. The cartridge lens cap 110 may have adiameter of between about 5-30 mm, between about 5.5-28 mm, betweenabout 6-26 mm, between about 6.5-24 mm, between about 7-22 mm, betweenabout 7.5-20 mm, between about 8-18 mm, between about 8.5-16 mm, betweenabout 9-14 mm, between about 9.5-12 mm, or any other diameter thatadvantageously facilitates use and collection of samples as disclosedherein. The cartridge lens cap 110 may have a height of between about3-26 mm, between about 4-24 mm, between about 5-22 mm, between about6-20 mm, between about 7-18 mm, between about 8-16 mm, between about9-14 mm, between about 10-12 mm, between about 26-30 mm, or any otherheight that advantageously facilitates use and collection of samples asdisclosed herein.

FIGS. 2A-2B illustrate exploded views of an embodiment of a samplecapture cartridge 100, e.g., the sample capture cartridge 100 of FIG.1A. The sample capture cartridge 100 of FIGS. 2A-2B includes a cartridgelens cap 110, a quantity of silica 120, a porous bowl 130, a cartridgedesiccant canister 140, a quantity of desiccant 150 and a cartridgedesiccant retainer 160. FIG. 1C illustrates how these components may fittogether.

FIGS. 4A-4G illustrate various views of an embodiment of a cartridgelens cap 110. FIG. 4A shows an embodiment of a cartridge lens cap 110having a lens cap window 112 surrounded by eight lens cap vents 114.FIG. 4B shows an embodiment of a cartridge lens cap 110 from the bottomsuch that at least three of the lens cap vents 114 and an undercut 116may be seen. FIG. 4C shows an embodiment of a cartridge lens cap 110from the bottom such that at least three of the lens cap vents 114 maybe seen. FIG. 4D shows a top view of an embodiment of a cartridge lenscap 110 having a lens cap window 112 surrounded by eight lens cap vents114. FIG. 4E shows a side view of an embodiment of a cartridge lens cap110 having a lens cap window 112 and several lens cap vents 114. FIG. 4Fshows a side view cut away of the cartridge lens cap 110 of FIG. 4Etaken alone line B-B and having a lens cap window 112 and several lenscap vents 114. FIG. 4G shows a bottom view of an embodiment of acartridge lens cap 110 having a lens cap window 112 and eight lens capvents 114.

One of ordinary skill in the art will understand that various featuresof the cartridge lens cap 110 may be changed. For example, certainfeatures of the cartridge lens cap 110 that may be changed include, butare not limited to: the size, shape, and number of the lens cap vents114; the size, shape, and thickness of the lens cap window 112; thediameter of the cartridge lens cap 110; and the height of the cartridgelens cap 110. The embodiment of the cartridge lens cap 110 shown inFIGS. 4A-4G includes eight lens cap vents 114. Other numbers of ventsmay be used. In some embodiments, the cartridge lens cap 110 has atleast 1 vent, at least 2 vents, at least 3 vents, at least 4 vents, atleast 5 vents, at least 6 vents, at least 7 vents, at least 8 vents, atleast 9 vents, at least 10 vents, at least 11 vents, at least 12 vents,between 12 and 20, or any number of vents that advantageouslyfacilitates sample collection as disclosed herein.

In some embodiments, each lens cap vent 114 is formed in a generallyradial fashion (e.g., the sides of each lens cap vent 114 are notparallel), as shown in FIGS. 4A & 4D. In some embodiments, each lens capvent 114 is between about 15 and 25 degrees wide. In other embodiments,each lens cap vent 114 is less than about 5 degrees wide, less thanabout 10 degrees wide, less than about 15 degrees wide, less than about20 degrees wide, less than about 25 degrees wide, less than about 30degrees wide, less than about 40 degrees wide, less than about 50degrees wide, less than about 60 degrees wide, less than about 70degrees wide, less than about 80 degrees wide, less than about 90degrees wide, or any other degree of width that advantageouslyfacilitates sample collection as disclosed herein. In some embodiments,each lens cap vent 114 is formed as a notch in the corner of thecartridge lens cap 110 (e.g., the sides of each lens cap vent 114 areparallel, or substantially parallel).

In some embodiments each lens cap vent 114 has three sides (e.g., is atrapezoidal cut or void in the edge of the cartridge lens cap 110). Inother embodiments, each lens cap vent 114 has only two sides (e.g., is av-shaped cut or void in the edge of the cartridge lens cap 110).

In some embodiments, such as the embodiment shown in FIG. 4D, the lenscap vents 114 are spaced evenly around the edge of the cartridge lenscap 110 (e.g., about every 45 degrees). In other embodiments, the lenscap vents 114 are grouped in patterns. In some embodiments, the lens capvents 114 are arranged in patterns so as to facilitate spiral outflow offluid from the interior of cartridge lens cap 110 of the sample capturecartridge 100 (as is disclosed herein). In some embodiments, the lenscap vents 114 are arranged in patterns so as to facilitate turbulentoutflow of fluid from the interior of cartridge lens cap 110 of thesample capture cartridge 100 (as is disclosed herein).

In some embodiments, the lens cap vents 114 are formed at asubstantially right angle with respect to the lens cap window 112, asshown in FIG. 4F. In some embodiments, the lens cap vents 114 are cut orformed obliquely in the edge of the cartridge lens cap 110 (rather thanradially) to facilitate spiral outflow of fluid from the interior of thecartridge lens cap 110 of the sample capture cartridge 100. In someembodiments, the lens cap vents 114 are cut or formed obliquely in theedge of the cartridge lens cap 110 (rather than radially) to facilitateturbulent outflow of fluid from the interior of the cartridge lens cap110 of the sample capture cartridge 100.

In some embodiments, such as the embodiment shown in FIG. 4F, the lenscap vents 114 have a vertical depth (e.g., from the top of the cartridgelens cap 110 to the base of each lens cap vent 114. Along with otherfeatures of the cartridge lens cap 110, the depth of the lens cap vents114 may define the size of the various lens cap vents 114. In someembodiments, the depth of the lens cap vents 114 is about 1 mm. In someembodiments, the depth of the lens cap vents 114 is in the range ofbetween about 0.01-4 mm, between about 0.05-3.8 mm, between about0.1-3.6 mm, between about 0.15-3.4 mm, between about 0.2-3.2 mm, betweenabout 0.25-3 mm, between about 0.30-2.8 mm, between about 0.35-2.6 mm,between about 0.40-2.4 mm, between about 0.45-2.2 mm, between about0.5-2 mm, between about 0.55-1.8 mm, between about 0.6-1.6 mm, betweenabout 0.65-1.4 mm, between about 0.7-1.2 mm, between about 0.75-1, orany other depth that advantageously facilitates airflow through thesample capture cartridge 100 and/or analysis of a sample through thelens cap window 112 as disclosed herein.

As shown in FIGS. 4A, 4D, 4F, and 4G, the top of the cartridge lens cap110 may include a lens cap window 112. The lens cap window 112 may beapproximately in the center of the top of the cartridge lens cap 110. Asis discussed herein, the lens cap window 112 may be used in an opticalanalysis of a sample (e.g., a photosensor measures a change in lightreflectance of a substance held behind the lens cap window 112). Forexample, various embodiments of base units may use photosensors oroptical sensors to sense or detect one or more optical characteristicsthrough the lens cap window 112 (e.g., an optical characteristic of thesilica 120 or a blended bowl). As such, in some embodiments, the lenscap window 112 may have a high degree of transparency. As used herein,transparency is the amount of light that passes through a barrier (e.g.,the lens cap window 112)—that is to say the total amount of lightsubtracting the amount of light reflected by the barrier and subtractingthe amount of light absorbed by the barrier.

In some embodiments, the lens cap window 112 has a transparency to thewavelength of light being measured (e.g., some materials have differenttransparencies to different wavelengths of light) of at least about 60%,at least about 65% at least about 70% at least about 75%, at least about80%, at least about 82.5%, at least about 85%, at least about 86%, atleast about 87%, at least about 88%, at least about 89%, at least about90%, at least about 92%, at least about 93%, at least about 94%, atleast about 95%, at least about 96%, at least about 97%, at least about98%, at least about 99%, or any of amount of transmittance thatadvantageously facilitates analysis of a sample through the lens capwindow 112 as disclosed herein. Of course, a lens cap window 112 havinga transmission of less than about 60% may be used; however, one ofordinary skill in the art will understand that other parameters of thesystem may need to be adjusted to compensate for the losses due toreflectance and absorbance by the lens cap window 112.

As shown in FIG. 1B, the lens cap window 112 may be circular. The lenscap window 112 may have other shapes. For example, the lens cap window112 may have the same number of sides as the cartridge lens cap 110 ofwhich it is a part (e.g., a four-sided cartridge lens cap 110 may have afour-sided lens cap window 112, and an eight-sided cartridge lens cap110 may have an eight-sided lens cap window 112). In some embodiments,the lens cap window 112 forms the entire top of the cartridge lens cap110 (e.g., the at least one lens cap vent 114 is cut into or formed inan edge of the lens cap window 112 that forms the top of the cartridgelens cap 110).

As shown in FIG. 4F, the lens cap window 112 has a thickness. In someembodiments, the thickness of the lens cap window 112 is less than thedepth (from top to bottom) of the lens cap vents 114: in that way, thethickness of the lens cap window 112 and the vertical depth of the lenscap vents 114 defines the thickness of the lens cap vents 114 (e.g., thesize of the lens cap vents 114 may be defined by the width of each lenscap vent 114, the vertical depth of each lens cap vent 114, the radialdepth of each lens cap vent 114, and the thickness of the lens capwindow 112). In some embodiments, the thickness of the lens cap window112 is about 1 mm. In some embodiments, the thickness of the lens capwindow 112 is in the range of between about 0.5-3 mm, between about0.55-2.8 mm, between about 0.6-2.6 mm, between about 0.65-2.4 mm,between about 0.7-2.2 mm, between about 0.75-2 mm, between about 0.8-1.8mm, between about 0.85-1.6 mm, between about 0.9-1.4 mm, between about0.95-1.2 mm, or any other thickness that advantageously facilitatesairflow through the sample capture cartridge 100 and/or analysis of asample through the lens cap window 112 as disclosed herein.

As best seen in FIGS. 4D, 4F and 4F, in some embodiments, the lens capvents 114 are cut radially into the top of the cartridge lens cap 110deeper than the thickness of the side wall of the cartridge lens cap110. In some embodiments, the lens cap vents 114 are cut into or formedin only the sidewall of the cartridge lens cap 110 (e.g., they do notextend into the top of the cartridge lens cap 110). In such embodiments,the top of the cartridge lens cap 110 may approximately resemble a diskset on a crenulated cylinder (e.g., in this case, the lens cap vents 114would exit only to the “side of the cartridge lens cap 110 rather thanalso forming an exit on/from the top of the cartridge lens cap 110). Insome embodiments, the entire top of the cartridge lens cap 110 is formedout of the lens cap window 112. In some embodiments, the top of thecartridge lens cap 110 is a solid disc (e.g., no lens cap vent 114 iscut/formed into the top, but is rather cut/formed into the side of thecartridge lens cap 110) and the lens cap window 112 is only in thecenter of the top of the cartridge lens cap 110.

The cartridge lens cap 110 may be configured to accept and hold theporous bowl 130. To hold the porous bowl 130, the cartridge lens cap 110may have a retention or holding feature on its inner wall. In someembodiments, the cartridge lens cap 110 may have a continuous or partialledge or step on its inner wall. For example, the cartridge lens cap 110may have a continuous ramped step (e.g., ramped from the bottom, andflat on the top) that is spaced a distance from the inner surface of thetop of the cartridge lens cap 110 substantially equal to the height ofthe porous bowl 130. Such a continuous ramped step may have a maximumwidth of about 0.13 mm. In other embodiments, a continuous ramped stepmay have a maximum width in the range of about 0.05-0.5 mm. In someembodiments, the retention or holding feature may not extend around theentirety of the cartridge lens cap 110. In some embodiments, as shown inFIG. 4B, the retention or holding feature may comprise one or moreundercuts 116. The undercuts 116 may be present with or without acontinuous or discontinuous ramped step. The undercut 116, as shown inFIG. 4B, may be a partial conical surface with a flat upper surfacefacing the top of the cartridge lens cap 110. Undercuts 116 may augmentor replace a continuous or partial smaller retention or holding feature.In some embodiments, the cartridge lens cap 110 has no retention orholding feature and retains the porous bowl 130 through friction. Inother embodiments, the porous bowl 130 is held within the cartridge lenscap 110 by the top surface of the cartridge desiccant canister 140pushing up against the bottom of the porous bowl 130 which holds the topsurface of the porous bowl 130 against the inner surface of the top ofthe cartridge lens cap 110.

FIGS. 4H-4J illustrate various views of an embodiment of a two-partcartridge lens cap 110. The two-part cartridge lens cap 110 may besimilar in structure and function to the other various embodiments ofcartridge lens caps 110 disclosed herein, such as the cartridge lens cap110 of FIGS. 4A-4G. While some features of the two-part cartridge lenscap 110 may be the same or identical to those other cartridge lens caps110 disclosed herein, they need not be the same or even similar. Likeother embodiments of the cartridge lens cap 110 disclosed herein, thetwo-part cartridge lens cap 110 may include a lens cap window 112 and atleast one lens cap vent 114.

The cartridge lens cap 110 shown in FIGS. 4H-4J includes a cartridgelens cap upper portion 111 and a cartridge lens cap lower portion 113.The cartridge lens cap upper portion 111 may have an engagement portionthat couples the cartridge lens cap upper portion 111 to the cartridgelens cap lower portion 113. As shown in FIGS. 4H-4J, the engagementportion may comprise a foot 117 on the cartridge lens cap upper portion111 and an undercut 118 on the cartridge lens cap lower portion 113, inthe wall, e.g., the inner lateral wall, of the cartridge lens cap lowerportion 113. Other different types of engagement or coupling portionsmay be used, including, but not limited to, threads, friction fit, etc.

In some embodiments, the engagement portion of the cartridge lens cap110 includes foot 117 extending downwards from the cartridge lens capupper portion 111 and extending around the cartridge lens cap upperportion 111. In some embodiments, the foot 117 extends substantially theentire way around the cartridge lens cap upper portion 111, e.g., adistance of about 360°. In some embodiments, the foot 117 extends aroundthe cartridge lens cap upper portion 111 less than about 360°. In someembodiments, the foot 117 comprises a plurality of distinct feet, e.g.,multiple downward protrusions, rather than a single ring. In someembodiments, the foot 117 comprises a number of feet 117 between about3-18, between about 4-16, between about 5-14, between about 6-12, andbetween about 7-10.

In some embodiments, the cartridge lens cap upper portion 111 comprisesan upper portion mating surface 170 surrounding the foot 117. The upperportion mating surface 170 may be a substantially level or flat surfaceconfigured to mate with, e.g., closely mate with, a correspondingsurface on the cartridge lens cap lower portion 113.

In some embodiments, the undercut 118 of the cartridge lens cap lowerportion 113 is a mirror image or negative of the foot 117 of thecartridge lens cap upper portion 111. In this way, the foot 117 may“snap” into the undercut 118 of the cartridge lens cap lower portion113. In embodiments in which the cartridge lens cap upper portion 111has more than one foot 117, the undercut 118 of the cartridge lens caplower portion 113 may include protrusions in the undercut 118 to indexthe cartridge lens cap upper portion 111 with respect to the cartridgelens cap lower portion 113. In this way, exacting alignment of thecartridge lens cap upper portion 111 with respect to the cartridge lenscap lower portion 113 may be reproducibly achieved.

In some embodiments, the cartridge lens cap lower portion 113 comprisesa lower portion mating surface 180 on its uppermost surface. The lowerportion mating surface 180 may be a substantially level or flat surfaceconfigured to mate with, e.g., closely mate with, a correspondingsurface on the cartridge lens cap upper portion 111. For example, thelower portion mating surface 180 of the cartridge lens cap lower portion113 may be configured to mate with the upper portion mating surface 170of the cartridge lens cap upper portion 111. In some embodiments, thelower portion mating surface 180 may be configured to substantiallysealingly mate with the upper portion mating surface 170 of thecartridge lens cap upper portion 111 when the cartridge lens cap upperportion 111 and the cartridge lens cap lower portion 113 are engaged(e.g., when the foot 117 engages the undercut 118).

In some embodiments, the cartridge lens cap lower portion 113 includes ashelf 115 extending radially inward below the undercut 118. The shelf115 may serve as a surface against which the foot 117 of the cartridgelens cap upper portion 111 may abut when fully in place in the undercut118. In some embodiments, the shelf 115 extends radially inward past theinnermost surface of the foot 117. In this way, the shelf 115 may alsosupport a porous bowl 130, holding the porous bowl 130 in the cartridgelens cap 110 between the cartridge lens cap upper portion 111 and thecartridge lens cap lower portion 113.

FIG. 4I shows a cartridge lens cap upper portion 111 engaged with acartridge lens cap lower portion 113, such that the foot 117 has fullyengaged the undercut 118 and is abutting the shelf 115. FIG. 4J shows anassembled cartridge lens cap 110, including cartridge lens cap upperportion 111, a cartridge lens cap lower portion 113, and a porous bowl130 held between the two. As can be seen, the shelf 115 of the cartridgelens cap lower portion 113 supports the porous bowl 130 and holds itsecurely within the cartridge lens cap upper portion 111.

A two-piece cartridge lens cap 110 may facilitate manufacture. In someembodiments, the cartridge lens cap 110 is manufactured by first placinga quantity of silica 120 in a porous bowl 130, which is placed on astable and/or flat surface. A cartridge lens cap upper portion 111 isthen placed in friction fit over the porous bowl 130. As can be seen inFIG. 4J, when the porous bowl 130 is fully in place within the cartridgelens cap upper portion 111, the bottom of the porous bowl 130 and thebase of the foot 117 are substantially aligned. Therefore, the cartridgelens cap upper portion 111 can be installed over the porous bowl 130with some force without risking damage to the porous bowl 130. Thecartridge lens cap upper portion 111 may hold the porous bowl 130 byfriction, e.g., the inner lateral walls of the cartridge lens cap upperportion 111 may engage the outer lateral walls of the porous bowl 130such that the porous bowl 130 will not easily slide out of the cartridgelens cap upper portion 111 once installed. After the porous bowl 130 isinstalled in the cartridge lens cap upper portion 111, the cartridgelens cap upper portion 111 and the cartridge lens cap lower portion 113may be engaged. As the porous bowl 130 is securely engaged with thecartridge lens cap upper portion 111, the construct of the cartridgelens cap upper portion 111 and the porous bowl 130 may be introduced tothe cartridge lens cap lower portion 113 right-side-up (as shown in FIG.4J) or upside-down. The construct of the porous bowl 130 and thecartridge lens cap upper portion 111 may simply be snapped into placewithin the cartridge lens cap lower portion 113 to complete thetwo-piece 110.

FIGS. 5A-5F illustrate various views of an embodiment of a porous bowl130 that may be used in conjunction with the various systems and methodsdisclosed herein. FIG. 5A illustrates an embodiment of a porous bowl 130from the side. FIG. 5B illustrates a side view cut-away of the porousbowl 130 of FIG. 5A taken along line C-C and showing the porous bowl's130 bowl wall 132 and bowl base 134. FIG. 5C shows a top-biasedthree-quarters view of an embodiment of a porous bowl 130. FIG. 5D showsa top-biased three-quarters view of another embodiment of a porous bowl130. FIG. 5E shows a top view of an embodiment of a porous bowl 130.FIG. 5F shows a bottom view of an embodiment of a porous bowl 130.

In some embodiments, the porous bowl 130 may be configured in a bowlshape. However, reference to this element as a bowl should not limit thescope of this disclosure. The porous element or member (e.g., bowl) mayhave any of a number of other shapes. For example the porous element ormember (e.g., the porous bowl) may be a disc, a frit, a molded solid, asolid, a molded shape, a slice, etc.

The porous bowl 130 may be formed to match an inner surface of acartridge lens cap 110. For example, the porous bowl 130 shown in FIGS.5A-5F is configured to fit within a cartridge lens cap 110 having asubstantially right angle where the side-wall(s) (e.g., the cylindricalside wall) of the cartridge lens cap 110 meet the top surface of thecartridge lens cap 110. The porous bowl 130 and the cartridge lens cap110 may be configured to closely match (e.g., the porous bowl 130 is anegative of an internal surface of the cartridge lens cap 110) so thatthe porous bowl 130 prevents a substance or material (e.g., silica 120)contained within the porous bowl 130 from exiting the porous bowl 130and cartridge lens cap 110 through the lens cap vents 114. In someembodiments, the porous bowl 130 may have rounded corners (e.g., arounded external corner(s) matching a rounded internal corner(s) on aninterior surface of the cartridge lens cap 110). While the porous bowl130 is described with reference to the accompanying figures, one ofordinary skill in the art will understand that various features of theporous bowl 130 may be changed.

The porous bowl 130 may have a diameter, most simply seen in FIG. 5F.The diameter of the porous bowl 130 may be selected to closely match aninternal diameter of the cartridge lens cap 110. It may be desirablethat the porous bowl 130 fit snugly, tightly, immovably, or fixedlywithin the cartridge lens cap 110. The diameter of the porous bowl 130may be between about 8-9 mm. In other embodiments, the diameter of theporous bowl 130 is between about 5-30 mm, between about 5.5-28 mm,between about 6-26 mm, between about 6.5-24 mm, between about 7-22 mm,between about 7.5-20 mm, between about 8-18 mm, between about 8.5-16 mm,between about 9-14 mm, between about 9.5-12 mm, or any other diameterthat advantageously facilitates use and collection of samples asdisclosed herein.

The porous bowl 130 may have a height, most simply seen in FIGS. 5A-5B.The bowl's height may be from the underside of the bowl base 134 to thetop of the bowl wall 132. In some embodiments, the height of the porousbowl 130 is about 2 mm. In other embodiments, the height of the porousbowl 130 is between about 0.5-3 mm, between about 0.55-2.8 mm, betweenabout 0.6-2.6 mm, between about 0.65-2.4 mm, between about 0.7-2.2 mm,between about 0.75-2 mm, between about 0.8-1.8 mm, between about0.85-1.6 mm, between about 0.9-1.4 mm, between about 0.95-1.2 mm, or anyother height that advantageously facilitates use and collection ofsamples as disclosed herein.

The porous bowl 130 may have a bowl depth, most simply seen in FIG. 5B.The bowl depth may be from the top side of the bowl base 134 to the topof the bowl wall 132. In some embodiments, the bowl depth is about 0.8mm. In other embodiments, the bowl depth is in the range of betweenabout 0.01-2.8 mm, between about 0.05-2.6 mm, between about 0.1-2.4 mm,between about 0.15-2.2 mm, between about 0.2-2 mm, between about0.25-1.8 mm, between about 0.30-1.6 mm, between about 0.35-1.4 mm,between about 0.40-1.2 mm, between about 0.45-1 mm, or any other depththat advantageously facilitates airflow through the sample capturecartridge 100 and/or analysis of a sample through the lens cap window112 as disclosed herein.

As will be explained in more detail herein, the porous bowl 130 maycontain a reactant that collects and/or reacts with a sample and thatexperiences a physical change that may by assessed or measured throughthe lens cap window 112. Thus, it is desirable that the porous bowl 130permit fluid flow therethrough. One of ordinary skill in the art willunderstand that the pore size of the porous bowl 130 is dependent on atleast two factors, including, but not limited to: 1) the necessary fluidflow rate through the porous bowl 130 (e.g., through the sample capturecartridge 100) (it will be easily understood that in some embodimentsthe porous bowl 130 is the individually greatest restriction to fluidflow through the sample capture cartridge 100) and 2) the particle sizethat must be held by the porous bowl 130 (e.g., the particle size of thesilica 120 material). Stated differently, fluid flow rate through thesample capture cartridge 100 may be limited by the porous bowl 130 and,more specifically, by the pore size of the porous bowl 130.Additionally, the material contained within the porous bowl 130 may havea quite small particle size, and it may be desirable to have a pore sizeof the porous bowl 130 that prevents all or substantially all of thematerial contained within the porous bowl 130 from passing through thebowl base 134 or bowl wall 132 of the porous bowl 130 (e.g., it may bedesirable to avoid the porous bowl 130 acting like a sieve to thematerial it contains).

In some embodiments, the porous bowl 130 has a pore size of about 130μm. In some embodiments, the porous bowl 130 has a pore size less thanabout 250 μm. In some embodiments, the porous bowl 130 has a pore sizein the range of between about 5-400 μm, between about 10-380 μm, betweenabout 15-360 μm, between about 20-340 μm, between about 25-320 μm,between about 30-300 μm, between about 35-280 μm, between about 40-260μm, between about 45-240 μm, between about 50-220 μm, between about55-200 μm, between about 60-180 μm, between about 65-175 μm, betweenabout 70-170 μm, between about 75-165 μm, between about 80-160 μm,between about 85-155 μm, between about 90-150 μm, between about 95-145μm, between about 100-140 μm, between about 105-135 μm, between about110-130 μm, between about 115-125 μm, or any other pore size that bothstrikes an advantageous balance between retaining any particle(s) withinthe porous bowl 130 (e.g., preventing exit of the substance intended tobe held within the bowl) and allowing the desired fluid flow ratethrough the porous bowl 130.

In some embodiments, the porous bowl 130 has dimensions and pore sizethat permits a flow rate through the porous bowl 130 of between about300-750 ml/min (e.g., the flow rate may be due to or under the pressureof a user blowing into a device holding the sample capture cartridge anddirecting the breath into and through the cartridge). In someembodiments, the porous bowl 130 is configured to permit a flow ratethrough the porous bowl 130 of between about 50-7000 ml/min, betweenabout 75-6750 ml/min, between about 100-6500 ml/min, between about125-6250 ml/min, between about 150-6000 ml/min, between about 175-5750ml/min, between about 200-5500 ml/min, between about 225-5250 ml/min,between about 250-5000 ml/min, between about 275-4750 ml/min, betweenabout 300-4500 ml/min, between about 325-4250 ml/min, between about350-4000 ml/min, between about 375-3750 ml/min, between about 400-3500ml/min, between about 425-3250 ml/min, between about 450-3000 ml/min,between about 475-2750 ml/min, between about 500-2500 ml/min, betweenabout 525-2250 ml/min, between about 550-2000 ml/min, between about575-1750 ml/min, between about 600-1500 ml/min, between 625-1250 ml/min,between about 650-1000 ml/min, between about 675-750 ml/min, or anyother flow rate that facilitates collection of sample from a fluidflowing through the sample capture cartridge 100 as disclosed herein. Insome embodiments, the porous bowl 130 is configured to permit a flowrate through the porous bowl 130 of between about 7000-10000 ml/min.

In some embodiments, the porous bowl 130 is configured to hold amaterial (e.g., silica beads) having an average particle size of about80 μm. In some embodiments, the porous bowl 130 is configured to hold amaterial having an average particle size of greater than about 40 μm,greater than about 45 μm, greater than about 50 μm, greater than about55 μm, greater than about 60 μm, greater than about 65 μm, greater thanabout 70 μm, greater than about 75 μm, greater than about 80 μm, greaterthan about 85 μm, greater than about 90 μm, greater than about 95 μm,greater than about 100 μm, greater than about 110 μm, greater than about120 μm, greater than about 130 μm, greater than about 140 μm, greaterthan about 150 μm, greater than about 160 μm, greater than about 170 μm,greater than about 180 μm, greater than about 190 μm, greater than about200 μm, greater than about 220 μm, greater than about 240 μm, greaterthan about 260 μm, greater than about 280 μm, greater than about 300 μm,greater than about 320 μm, greater than about 340 μm, greater than about360 μm, greater than about 380 μm, greater than about 400, or any othersize of particle that advantageously facilitates sample capture andanalysis as disclosed herein. In some embodiments, the pore size of theporous bowl 130 is larger (e.g., only slightly larger) than the particlesize of the material to be contained within the porous bowl 130. In someembodiments, the pore size of the porous bowl 130 is smaller than theparticle size of the material to be contained within the porous bowl130.

The material held within the porous bowl 130 may be an unreactive basematerial or substrate, such as silica, silica gel, silica wool, glass,nitrocellulous, a sodium silicate derivate, or metal oxide, to which areactant has been attached to cause the base material to becomefunctionalized. The base material may be in the form of particles ofvarious configurations (e.g., beads), although this need not be thecase. In some embodiments the material contained within the porous bowl130 is silica 120. The silica 120 may be functionalized with an amine(e.g., aminated). For example, an amine (which may later react with asample of interest, e.g., an analyte of interest) may be bound to thesurface of the silica beads or particles.

In some embodiments, the particles comprising the silica 120 aresubstantially round or spherical and have a particle size (e.g., anaverage particle size) of about 50 μm. In some embodiments the particlescomprising the silica 120 have a particle size (e.g., an averageparticle size of less than about 300 μm, less than about 280 μm, lessthan about 260 μm, less than about 240 μm, less than about 220 μm, lessthan about 200 μm, less than about 180 μm, less than about 160 μm, lessthan about 140 μm, less than about 120 μm, less than about 100 μm, lessthan about 90 μm, less than about 80 μm, less than about 70 μm, lessthan about 60 μm, less than about 50 μm, less than about 40 μm, lessthan about 30 μm, less than about 20, or any other diameter thatadvantageously facilitates sample flow through the silica 120 andinteraction of the silica 120 with the analyte of interest containedwithin the fluid sample. In some embodiments, the particles comprisingthe silica 120 have a particle size (e.g., an average particle size inthe range of between about 37-53 μm, between about 53-88 μm, or betweenabout 88-105 μm.

In some embodiments, the quantity of silica 120 may fill the porous bowl130 more than about 50%, more than about 55%, more than about 60%, morethan about 60%, more than about 70%, more than about 75%, more thanabout 80%, more than about 85%, more than about 90%, more than about95%, or any other amount that facilitates capture/collection andanalysis of a sample as disclosed herein.

In some embodiments, the volume of silica 120 contained within theporous bowl 130 is less than about 5 ml, less than about 4.5 ml, lessthan about 4 ml, less than about 3.5 ml, less than about 3 ml, less thanabout 2.5 ml, less than about 2 ml, less than about 1.5 ml, less thanabout 1.4 ml, less than about 1.3 ml, less than about 1.2 ml, less thanabout 1.1 ml, less than about 1 ml, less than about 0.9 ml, less thanabout 0.8 ml, less than about 0.7 ml, less than about 0.6 ml, less thanabout 0.5 ml, less than about 0.4 ml, less than about 0.3 ml, less thanabout 0.2 ml, less than about 0.1 ml, or any other volume thatfacilitates capture/collection and analysis of a sample as disclosedherein.

In some embodiments, rather than using silica beads or particles, otherchemistry substrates or base materials are used, such as sodium silicatederivates and/or silica/quartz wool. For example, a 4″×1″ strip ofsilica wool can put in a solution of 1.6 ml APTES+3.2 ml propanol+3.2 mlsulfuric acid and heated to 80° C. for 2 hours and then 110° C. for 1hour. The result is silica wool conjugated with primary amine. Thesesubstrates may have different geometries, such as planar, sheets, etc.(e.g., they may be cut or formed into disks that can be place in theporous bowl 130).

FIGS. 6A-6C illustrate various views of an embodiment of a cartridgedesiccant canister 140. FIG. 6A shows an embodiment of a cartridgedesiccant canister 140 from the top, such that the inside of thecanister cavity 144 and the several canister sample ports 142 may beseen. FIG. 6B shows an embodiment of a cartridge desiccant canister 140from the bottom. FIG. 6C illustrates a side view cut-away of thecartridge desiccant canister 140 of FIG. 6B taken along line D-D andshowing the canister cavity 144 and cross-sections of various canistersample ports 142. The canister sample ports 142 direct sample fluid fromthe opening into the canister cavity 144 and towards the porous bowl 130and the silica 120 it contains. Therefore, the canister sample ports 142may advantageously have characteristics (e.g., shape, size, direction,etc.) that promote thorough and efficient mixing of the sample fluidwith the silica 120 contained within the porous bowl 130. In someembodiments, such efficient mixing is achieved by inducing turbulentflow of the sample fluid. In some embodiments, the canister sample ports142 are shaped, arranged, and oriented to increase the turbulence offluid flow and/or mixing of the sample fluid with the silica 120contained in the porous bowl 130.

In some embodiments, as shown in FIGS. 6A and 6B, the cartridgedesiccant canister 140 may have 12 individual canister sample ports 142.In some embodiments, the cartridge desiccant canister 140 may havedifferent numbers of canister sample ports 142. For example, thecartridge desiccant canister 140 may have one canister sample port 142.The cartridge desiccant canister 140 may have less than about 2 canistersample ports 142, less than about 4 canister sample ports 142, less thanabout 6 canister sample ports 142, less than about 8 canister sampleports 142, less than about 10 canister sample ports 142, less than about15 canister sample ports 142, less than about 20 canister sample ports142, less than about 25 canister sample ports 142, less than about 30canister sample ports 142, less than about 35 canister sample ports 142,less than about 40 canister sample ports 142, less than about 45canister sample ports 142, less than about 50 canister sample ports 142,or any other number of canister sample ports 142 that promotes fluidflow through the sample capture cartridge 100 and efficient mixing ofthe fluid (e.g., the fluid containing the sample with the silica 120contained in the porous bowl 130).

With continued reference to FIGS. 6A and 6B, the canister sample ports142 may be round. However, the canister sample ports 142 may have othershapes. In some embodiments, the canister sample ports 142 aretriangular, rectangular, pentagonal, or hexagonal. Any shape of canistersample ports 142 may be used that advantageously promotes fluid flowthrough the sample capture cartridge 100 and efficient mixing of thefluid (e.g., the fluid containing the sample with the silica 120contained in the porous bowl 130). In some embodiments, connected shapesare used as canister sample ports 142, e.g., “plus” (e.g., “+”) shapedholes, linear shaped holes (e.g., “−”), etc. In some embodiments, thecanister sample ports 142 are distributed evenly across the surfacedefining the bottom of the canister cavity 144. In some embodiments, thecanister sample ports 142 are oriented more toward the center of thesurface defining the bottom of the canister cavity 144 (e.g., increasein concentration closer to the center of the cartridge desiccantcanister 140).

As can be seen in FIG. 6C, the canister sample ports 142 may be orientedsubstantially vertically through the cartridge desiccant canister 140.That is to say that the canister sample ports 142 may extend through thecartridge desiccant canister 140 at approximately a right angle to theportion of the cartridge desiccant canister 140 that forms the bottom ofthe canister cavity 144. In some embodiments, the canister sample ports142 extend through the cartridge desiccant canister 140 at an angle. Insome embodiments the canister sample ports 142 extend through thecartridge desiccant canister 140 at an angle of less than about 2degrees off perpendicular, less than about 4 degrees off perpendicular,less than about 6 degrees off perpendicular, less than about 8 degreesoff perpendicular, less than about 10 degrees off perpendicular, lessthan about 15 degrees off perpendicular, less than about 20 degrees offperpendicular, less than about 25 degrees off perpendicular, less thanabout 30 degrees off perpendicular, less than about 35 degrees offperpendicular, less than about 40 degrees of perpendicular, less thanabout 45 degrees off perpendicular, or any other angle thatadvantageously promotes fluid flow through the sample capture cartridge100 and efficient mixing of the fluid (e.g., the fluid containing thesample with the silica 120 contained in the porous bowl 130). In someembodiments, angled canister sample ports 142 may advantageously promotehelical or spiral fluid flow through the canister cavity 144 and improveturbulent flow and/or missing of the sample fluid with the silica 120.

Some embodiments of the cartridge desiccant canister 140 may include acartridge desiccant canister 140 to prevent moisture transfer to theporous bowl 130. The canister cavity 144 of the cartridge desiccantcanister 140 may have a depth of about 3.9 mm. In some embodiments thecanister cavity 144 of the cartridge desiccant canister 140 has a depthless than about 12 mm, less than about 11 mm, less than about 10 mm,less than about 9 mm, less than about 8 mm, less than about 7 mm, lessthan about 6 mm, less than about 5 mm, less than about 4 mm, less thanabout 3 mm, less than about 2 mm, less than about 1 mm, or any otherdepth that inhibits or minimizes moisture transfer to the porous bowl130.

In some embodiments, such as shown in FIG. 6C, nothing is contained inthe canister cavity 144 (e.g., it is empty space). The absence of anymaterial in the canister cavity 144 may advantageously promote directtransfer of fluid flow from the canister sample ports 142 to the porousbowl 130, through the bowl base 134 and into the silica 120 containedwithin the porous bowl 130. That is, an empty canister cavity 144 mayallow better fluid flow and mixing to occur in the silica 120 becausethe fluid flow leaving the canister sample ports 142 is not impeded by amaterial. However, an additional layer of material to absorb excessmoisture (e.g., when analyzing particularly moist samples) may bedesirable. In some embodiments, an absorbent material is placed in thecanister cavity 144 (e.g., cotton or other fibers in a looseagglomeration).

As shown in FIGS. 1C, and 2A-2B, the cartridge desiccant canister 140may contain a material to condition a sample-containing fluid before itexits the canister sample ports 142 and enters the porous bowl 130 toreact with the functionalized silica 120. In some embodiments, thecartridge desiccant canister 140 contains a quantity of desiccant 150.In some embodiments, the cartridge desiccant canister 140 contains anabsorbent disk.

In some embodiments the cartridge desiccant canister 140 contains avolume of desiccant 150 that may be measured in desiccant particles. Insome embodiments, the cartridge desiccant canister 140 contains about20-40 desiccant particles. In some embodiments, the cartridge desiccantcanister 140 contains between about 5-200 desiccant particles, betweenabout 10-270 desiccant particles, between about 15-240 desiccantparticles, between about 20-210 desiccant particles, between about25-180 desiccant particles, between about 30-150 desiccant particles,between about 35-120 desiccant particles, between about 40-190 desiccantparticles, between about 45-160 desiccant particles, between about50-130 desiccant particles, between about 55-100 desiccant particles,between about 60-70 desiccant particles, or any other number ofdesiccant particles that advantageously conditions a fluid sample priorto its interaction with the silica 120 contained within the porous bowl130.

In some embodiments the cartridge desiccant canister 140 contains aquantity of desiccant 150 that may be measured in mass, e.g.,milligrams. In some embodiments, the cartridge desiccant canister 140contains a mass of desiccant 150 in the range of between about 50-1800mg, between about 60-1750 mg, between about 70-1700 mg, between about80-1650 mg, between about 90-1600 mg, between about 100-1550 mg, betweenabout 110-1500 mg, between about 120-1450 mg, between about 130-1400 mg,between about 140-1350 mg, between about 150-1300 mg, between about160-1250 mg, between about 170-1200 mg, between about 180-1150 mg,between about 190-1100 mg, between about 200-1050 mg, between about210-1000 mg, between about 220-950 mg, between about 230-900 mg, betweenabout 240-850 mg, between about 250-800 mg, between about 260-750 mg,between about 270-700 mg, between about 280-650 mg, between about290-600 mg, between about 300-550 mg, between about 310-500 mg, betweenabout 320-450 mg, between about 330-400 mg, or between about 340-350 mg.In some embodiments, the cartridge desiccant canister 140 contains amass of desiccant 150 in the range of between about 160-180 mg, betweenabout 540-560 mg, or any other mass of desiccant 150 that advantageouslyconditions a fluid sample prior to its interaction with the silica 120contained within the porous bowl 130.

In some embodiments, the cartridge desiccant canister 140 may contain atleast one absorbent disk in addition to or in place of the desiccant150. The absorbent disk may be a cotton pad. In some embodiments, anabsorbent disk is placed above the desiccant 150 (e.g., between thedesiccant 150 and the canister sample ports 142). In some embodiments,an absorbent disk is placed below the desiccant 150 (e.g., between thedesiccant 150 and the cartridge desiccant retainer 160). In still otherembodiments, a first absorbent disk is placed above the desiccant 150(e.g., between the desiccant 150 and the canister sample ports 142) anda second absorbent disc is placed below the desiccant 150 (e.g., betweenthe desiccant 150 and the cartridge desiccant retainer 160). Anymaterials held within the cartridge desiccant canister 140 may be heldin place by a cartridge desiccant retainer 160.

FIGS. 7A-7C illustrate various views of an embodiment of a cartridgedesiccant retainer 160. FIG. 7A shows a top view of an embodiment of acartridge desiccant retainer 160. FIG. 7B shows a bottom view of anembodiment of a cartridge desiccant retainer 160. FIG. 7C shows a sidecut-away view of the cartridge desiccant retainer 160 of FIG. 7A, takenalong line E-E. The cartridge desiccant retainer 160 generally has adiameter, a thickness, and a plurality of desiccant retainer ports 164.In some embodiments, the cartridge desiccant retainer 160 also includesa desiccant retainer bevel 166 and/or a desiccant retainer notch 162.

The diameter of the cartridge desiccant retainer 160 may be just smallerthan an inner diameter of the cartridge desiccant canister 140. In someembodiments, the diameter of the cartridge desiccant retainer 160 isbetween about 8-9 mm. In other embodiments, the diameter of thecartridge desiccant retainer 160 is between about 5-30 mm, between about5.5-28 mm, between about 6-26 mm, between about 6.5-24 mm, between about7-22 mm, between about 7.5-20 mm, between about 8-18 mm, between about8.5-16 mm, between about 9-14 mm, between about 9.5-12 mm, or any otherdiameter that advantageously facilitates use and collection of samplesas disclosed herein.

In some embodiments, the thickness of the cartridge desiccant retainer160 is about 1 mm. In other embodiments, the thickness of the cartridgedesiccant retainer 160 is between about 0.2-3 mm thick, between about0.3-2.8 mm thick, between about 0.4-2.6 mm thick, between about 0.5-2.4mm thick, between about 0.6-2.2 mm thick, between about 0.7-2 mm thick,between about 0.8-1.8 mm thick, between about 0.9-1.6 mm thick, betweenabout 1-1.4 mm thick, between about 1.1-1.2 mm thick, or any otherthickness that advantageously facilitates use and collection of samplesas disclosed herein.

In some embodiments, the cartridge desiccant retainer 160 may be snapfit into the cartridge desiccant canister 140. As can be seen withreference to FIG. 6C, the cartridge desiccant canister 140 may include araised ridge on its inner surface to hold the cartridge desiccantretainer 160 in place. The desiccant retainer bevel 166 may facilitatethe cartridge desiccant retainer 160 slipping unidirectionally past theraised ridge on the inner surface of the cartridge desiccant canister140. In other embodiments, the cartridge desiccant retainer 160 may bethreaded into the cartridge desiccant canister 140. In yet otherembodiments, any other type of fixation may be used to hold thecartridge desiccant retainer 160 inside the cartridge desiccant canister140, e.g., glue, epoxy, friction, welding, bonding, etc.

As can be seen with reference to FIG. 7A-7B, the cartridge desiccantretainer 160 may have 12 individual desiccant retainer notches 162. Insome embodiments, the cartridge desiccant retainer 160 may havedifferent numbers of desiccant retainer ports 164. For example, thecartridge desiccant canister 140 may have one desiccant retainer port164. The cartridge desiccant canister 140 may have less than about 2desiccant retainer ports 164, less than about 4 desiccant retainer ports164, less than about 6 desiccant retainer ports 164, less than about 8desiccant retainer ports 164, less than about 10 desiccant retainerports 164, less than about 15 desiccant retainer ports 164, less thanabout 20 desiccant retainer ports 164, less than about 25 desiccantretainer ports 164, less than about 30 desiccant retainer ports 164,less than about 35 desiccant retainer ports 164, less than about 40desiccant retainer ports 164, less than about 45 desiccant retainerports 164, less than about 50 desiccant retainer ports 164, or any othernumber of desiccant retainer ports 164 that promotes fluid flow throughthe sample capture cartridge 100 and efficient mixing of the fluid(e.g., the fluid containing the sample with the silica 120 contained inthe porous bowl 130).

With continued reference to FIGS. 7A and 7B, the desiccant retainerports 164 may be round. However, the desiccant retainer ports 164 mayhave other shapes. In some embodiments, the desiccant retainer ports 164are triangular, rectangular, pentagonal, or hexagonal. Any shape ofdesiccant retainer ports 164 may be used that advantageously promotesfluid flow through the sample capture cartridge 100 and efficient mixingof the fluid (e.g., the fluid containing the sample with the silica 120contained in the porous bowl 130). In some embodiments, connected shapesare used as desiccant retainer ports 164, e.g., “plus” (e.g., “+”)shaped holes, linear shaped holes (e.g., “−”), etc. In some embodiments,the desiccant retainer ports 164 are distributed evenly across thecartridge desiccant retainer 160. In some embodiments, the desiccantretainer ports 164 are oriented more toward the center of the cartridgedesiccant retainer 160 (e.g., increase in concentration closer to thecenter of the cartridge desiccant retainer 160).

As can be seen in FIG. 7C, the desiccant retainer ports 164 may beoriented substantially vertically through the cartridge desiccantretainer 160. That is to say that the desiccant retainer ports 164 mayextend through the cartridge desiccant retainer 160 at approximately aright angle to the either the top surface of the cartridge desiccantretainer 160 or the bottom surface of the cartridge desiccant retainer160. In some embodiments, the desiccant retainer ports 164 extendthrough the cartridge desiccant retainer 160 at an angle. In someembodiments the desiccant retainer ports 164 extend through thecartridge desiccant retainer 160 at an angle of less than about 2degrees off perpendicular, less than about 4 degrees off perpendicular,less than about 6 degrees off perpendicular, less than about 8 degreesoff perpendicular, less than about 10 degrees off perpendicular, lessthan about 15 degrees off perpendicular, less than about 20 degrees offperpendicular, less than about 25 degrees off perpendicular, less thanabout 30 degrees off perpendicular, less than about 35 degrees offperpendicular, less than about 40 degrees of perpendicular, less thanabout 45 degrees off perpendicular, or any other angle thatadvantageously promotes fluid flow through the sample capture cartridge100 and efficient mixing of the fluid (e.g., the fluid containing thesample with the silica 120 contained in the porous bowl 130). In someembodiments, angled desiccant retainer ports 164 may advantageouslypromote helical or spiral fluid flow through the canister cavity 144 andimprove turbulent flow and/or missing of the sample fluid with thesilica 120. In some embodiments, the canister cavity 144 may include anumber of baffles, fins, vanes, wings, or other such structures on(e.g., attached to) an interior surface of the canister cavity 144 topromote turbulent, helical, spiral, or other mixing flow patterns. Forexample, the canister cavity 144 may have 4 baffles. In someembodiments, the canister cavity 144 includes between about 1 and 16baffles, between about 2 and 14 baffles, between about 3 and 12 baffles,between about 4 and 10 baffles, between about 5 and 8 baffles, or anyother number of baffles that advantageously facilitates turbulent,helical, spiral, or other mixing patterns.

With reference to both FIG. 7A and FIG. 6A, desiccant retainer ports 164in the cartridge desiccant retainer 160 are arranged in substantiallythe same pattern as the canister sample ports 142 in the cartridgedesiccant canister 140 (e.g., the cartridge desiccant retainer 160 hasthe same number of desiccant retainer ports 164 as the cartridgedesiccant canister 140 has canister sample ports 142). The cartridgedesiccant retainer 160 may be installed into the cartridge desiccantcanister 140 so that the desiccant retainer ports 164 of the cartridgedesiccant retainer 160 are intentionally substantially aligned (e.g.,aligned within 5 degrees) with the canister sample ports 142 of thecartridge desiccant canister 140. Alignment of the desiccant retainerports 164 with the canister sample ports 142 may be facilitated bymechanical alignment, e.g., embodiments in which the cartridge desiccantretainer 160 is installed into the cartridge desiccant canister 140using threads. In some embodiments, the cartridge desiccant retainer 160may be installed into the cartridge desiccant canister 140 so that thedesiccant retainer ports 164 of the cartridge desiccant retainer 160 areintentionally misaligned (e.g., more than 10 degrees off) with thecanister sample ports 142 of the cartridge desiccant canister 140.Misalignment of the desiccant retainer ports 164 of the cartridgedesiccant retainer 160 and the canister sample ports 142 of thecartridge desiccant canister 140 may advantageously improve turbulentmixing/flow of the sample-containing fluid and/or more complete sampleconditioning due to increased contact of the sample-containing fluidwith one or more sample-conditioning substances (e.g., desiccant and/orabsorbent pad(s)) within the cartridge desiccant canister 140.

In some embodiments, the cartridge desiccant retainer 160 has adifferent number of desiccant retainer ports 164 than the cartridgedesiccant canister 140 has canister sample ports 142. In someembodiments, the desiccant retainer ports 164 of the cartridge desiccantretainer 160 are arranged in a different pattern than the canistersample ports 142 of the cartridge desiccant canister 140. In someembodiments, the desiccant retainer ports 164 of the cartridge desiccantretainer 160 have a different shape(s) than the canister sample ports142 of the cartridge desiccant canister 140 (e.g., the desiccantretainer port 164 may be a single “+” shaped hole, while the cartridgedesiccant canister 140 contains multiple circular canister sample ports142). Some or all of these features may advantageously contribute to aturbulent flow pattern through part or all of the sample capturecartridge 100. One of ordinary skill in the art will readily understandthat various combinations of features, such as described herein, may beused to achieve a desired fluid flow path and mixing profile.

Turning to FIG. 1C, the cartridge lens cap 110 may be formed separatelyand fit onto the cartridge desiccant canister 140. In some embodiments,the cartridge lens cap 110 is removably attached/attachable to thecartridge desiccant canister 140. For example, the cartridge lens cap110 may be attached to the cartridge desiccant canister 140 usingthreads, friction, clips, detents, springs, j-hooks, etc. In otherembodiments, the cartridge lens cap 110 is fixedly attached/attachableto the cartridge desiccant canister 140. For example, the cartridge lenscap 110 may be attached to the cartridge desiccant canister 140 usingepoxies, glues, welding (e.g., friction welding, and/or other types ofwelding), cements, locking threads, clips, co-melting plastics, etc.

In some embodiments, the cartridge desiccant canister 140 is formed outof a softer material (e.g., polymer or plastic) to facilitate thecartridge lens cap 110 slipping over the top of the cartridge desiccantcanister 140. In some embodiments, the inner wall of the cartridge lenscap 110 and the outer wall of the upper portion of the cartridgedesiccant canister 140 have an angle (are slightly sloped or conical) tofacilitate simple and quick fitment of the cartridge lens cap 110 to thecartridge desiccant canister 140. In some embodiments, the outer wall ofthe cartridge desiccant canister 140 has an angle of about 92 degrees tothe horizontal. In some embodiments, the outer wall of the cartridgedesiccant canister 140 has an angle of less than about 100 degrees, lessthan about 99 degrees, less than about 98 degrees, less than about 98degrees, less than about 97 degrees, less than about 96 degrees, lessthan about 95 degrees, less than about 94 degrees, less than about 93degrees, less than about 92 degrees, less than about 91 degrees, or anyother angle that facilitate application and/or removal of the cartridgelens cap 110 from the sample capture cartridge 100.

Blended Bowl

Turning again to FIGS. 1C, 2A-2B, and 5A-5F, in some embodiments, theporous bowl 130 may be a bowl made of a porous plastic material thatpermits air flow therethrough, such as, but not limited to, a porouspolyethylene, porous polypropylene, porous polyvinylidene fluoride,porous polytetrafluoroethylene, porous ethyl vinyl acetate, porouspolycarbondates, porous nylons, porous polyurethanes, porouspolyethersulfones. In some embodiments, the porous bowl 130 may be abowl made of a porous polymer fiber material that permits air flowtherethrough, such as, but not limited to, polyethylene/polyesterpolymer fibers (e.g., bicomponent polyethylene sheath with polyestercore fibers (PE/PET)), and/or polyester/polyester polymer fibers (e.g.,bicomponent polyester sheath and polyester core fibers (PET/PET)). Insome embodiments, the porous bowl 130 is constructed out of ahydrophobic material.

As shown in FIG. 1C, the porous bowl 130 may contain a quantity of amaterial, e.g., silica beads 120. The silica 120 itself may beunreactive to the sample, but the silica 120 may be functionalized witha reactive moiety, receptor, reactor, etc. The functionalized silica 120may then absorb or react with an analyte of interest in a sample passedthrough the porous bowl 130 of the sample capture cartridge 100.

In embodiments in which the porous bowl 130 contains a quantity of afunctionalized material (e.g., functionalized silica particles) used tocapture an analyte of interest from a fluid sample, mixing may beparticularly important (e.g., mixing of the sample with and through thesilica 120 contained within the porous bowl 130). Mixing is one reason,among many potential reasons, that turbulent flow through the samplecapture cartridge 100 may be desirable. For example, without propermixing, there may be “hot spots” of analyte accumulation within thesilica 120 contained within the porous bowl 130. That is to say, withoutsufficient mixing, the analyte of interest will react only with thefunctionalized silica 120 that is reasonably close to the fluid sample'spath of least resistance through the sample capture cartridge 100.Sufficient mixing may allow an even reaction between the analyte ofinterest and the functionalized silica 120 contained within the porousbowl 130. When the reaction between the analyte of interest contained inthe fluid sample and the functionalized silica 120 is even, the samplemay advantageously be analyzed more accurately. For example, inembodiments in which the reaction ultimately causes a change in color ofthe silica 120 contained within the porous bowl 130, sufficient mixingmay produce an even medium color throughout the silica 120, butinsufficient mixing may produce spots of deep or dark color in some,higher flow, locations in the silica 120 and little to no color inother, lower flow, locations, in the silica 120.

The reaction of the analyte with the functionalized silica 120 mayproduce a measurable change in a parameter of the silica 120. In someembodiments the measurable change is a change in a color of thefunctionalized silica 120 (e.g., the functionalized silica 120 maychange color, may deepen in hue, may change in intensity, etc.). In someembodiments the measurable change is a change in temperature. In someembodiments, the measurable change is a change in volume. Any othermeasurable change may be used.

In some embodiments, no change is experienced or observed directly afterthe analyte of interest in the sample is passed through the samplecapture cartridge 100. In some embodiments, after the analyte ofinterest has been captured or separated from the rest of the sample,another substance, an interactant subsystem, such as a developersolution, may be added to the system to bring about or induce themeasurable change. The interactant subsystem may be, or include sodiumnitroprusside, dinitrophenylhydrazine, sodium dichromate,pararosaniline, bromophenol blue, dischloroisocyanourate, sodiumsalicylate, sodium dichromate, crystal violet, benzyl mercaptan, orcombinations thereof.

In some embodiments, the silica particles (or particles of another basematerial or substrate such as those mentioned above) may befunctionalized with an interactant that supports a single-step reactionwhich produces a measurable color change without the need to introduce adeveloper solution. In single-step cartridges for measuring acetone, theinteractant may include a complex including one or more metal ions andone or more primary amine molecules bound to the metal ions. The primaryamine molecules may be amino acid molecules with a primary amine sidechain (e.g. lysine, arginine), and the carboxylic acid group of theamino acid molecules may be bound to the metal ions. The complexincluding the metal ions and primary amine molecules may be furtherimmobilized to a base material, such as silica beads. Other interactantcompositions that support single-step reactions are known in the art.

In some embodiments, the porous bowl 130 is manufactured to integrallyand/or substantially homogeneously contain the functionalized basematerial (e.g., functionalized silica particles) to create a blendedbowl or structure. In such embodiments, the porous bowl 130 may retainits “bowl” shape. Or, the porous bowl 130 may be formed as a disc, puckor other shape (e.g., as it no longer needs to contain a volume ofsilica 120 within the porous bowl 130). Thus, although the term “bowl”or “blended bowl” is used throughout this description for illustrativepurposes, it should be understood that the blended structure need nothave a bowl shape, and may have any of a variety of shapes orconfigurations.

The blended bowl or structure may be formed of a porous reactive mediacomprising a polymeric infrastructure and a resin incorporating areactive chemistry configured to react with or bind to the analyte ofinterest in the fluid sample (e.g., breath sample) being evaluated. Theblended bowl may be synthesized utilizing a blended resin in asubstantially round or spherical configuration of the polymeric material(including but not limited to polyethylene) and functionalized reactivebeads (e.g., functionalized silica 120 beads, as disclosed herein). Insome embodiments, the porous bowl may be formed out of a functionalizedfused silica wool.

A blended bowl or structure may advantageously be formed out of resinparticles and functionalized or reactive particles in a mixture that isabout 50% resin particles. In some embodiments, a blended bowl may beformed out of resin particles and functionalized or reactive particlesin a mixture that is less than about 50% functionalized or reactiveparticles, less than about 45% functionalized or reactive particles,less than about 40% functionalized or reactive particles, less thanabout 35% functionalized or reactive particles, less than about 30%functionalized or reactive particles, less than about 25% functionalizedor reactive particles, less than about 20% functionalized or reactiveparticles, less than about 15% functionalized or reactive particles,less than about 10% functionalized or reactive particles, less thanabout 5% functionalized or reactive particles, less than about, or anyother percentage that advantageously facilitates sufficient capture ofan analyte of interest by the functionalized or reactive particles heldby the blended bowl.

In some embodiments, a blended bowl incorporates a quantity of desiccantin addition to the quantity of functionalized or reactive particles. Insome embodiments, a blended bowl may be formed out of resin particlesand functionalized or reactive particles as discussed here, with aquantity of desiccant in a mixture that is less than about 50%desiccant, less than about 45% desiccant, less than about 40% desiccant,less than about 35% desiccant, less than about 30% desiccant, less thanabout 25% desiccant, less than about 20% desiccant, less than about 15%desiccant, less than about 10% desiccant, less than about 5% desiccant,less than about 2.5% desiccant, or any other percentage thatadvantageously facilitates removal of excess moisture from a fluidsample.

Resin particles and functionalized or reactive particles may be formedinto a blended bowl, disc, or frit using a sintering process. Thesintering process may involve a die tool (e.g., a floating die) tomanufacture the blended bowl at temperatures in the range of about110-400° C., e.g., generally above the true melting point of thepolymeric material. Bonds between the materials contained in thereactive particles and resin particles may be formed during thesintering process. Alternative sintering techniques, e.g., known asselective laser sintering (SLS), may be used to form the blended bowl.For example, SLS may use a laser (e.g., operated in continuous mode) atvariable ranges of speed and power to obtain the appropriate energydensity per unit time in the fabrication of pore sizes and reactantdispersions throughout the blended bowl. Thermal treatment at highertemperatures may allow for aminated reactive beads to assiduouslycoagulate within the polymeric infrastructure via covalent bonding andgrafting at the interface.

In some embodiments, a blended bowl or structure may be inserted intothe cartridge lens cap 110. In some embodiments a blended bowl may bemechanically coupled (e.g., directly coupled) to the underside of thelens cap window 112, which may advantageously provide a degree ofsurface area augmentation.

In some embodiments, the blended bowl or structure is configured such asthe porous bowl 130, as disclosed herein. The blended bowl may beinstalled in the cartridge lens cap 110 such as shown in FIG. 1C, e.g.,with the “bowl” facing upwards (e.g., facing the lens cap window 112 ofthe cartridge lens cap 110). Alternatively, the blended bowl may beinstalled in the cartridge lens cap 110 opposite that shown in FIG. 1C,e.g., with the “bowl” facing downwards (e.g., the bowl base 134 of theporous bowl 130 facing the lens cap window 112 of the cartridge lens cap110). For example, the blended bowl may have a bowl-like (e.g., such asshown in FIGS. 5C-5D) configuration such that the outer edges, includingbut not limited to the bowl wall 132 and the bowl base 134. Suchbowl-like configurations may offer an advantageously increased (e.g., amaximum) surface area available for adhesion (e.g., secure adhesion) tothe inside surface of the lens cap window 112 of the cartridge lens cap110. In some embodiments, the cavity depth is influenced by the flowpath of the fluid sample during sample collection (e.g., containing ananalyte of interest) through the overall sample capture cartridge 100(e.g., into the cartridge desiccant canister 140, through the cartridgedesiccant retainer 160, through the desiccant 150, through the ports inthe upper surface of the cartridge desiccant canister 140, through thecanister cavity 144, etc.) to the outward surface of the blended bowl.

A blended bowl or structure as discussed herein may advantageouslysimplify, linearize, shorten, etc. the procedure or process formanufacturing a sample capture cartridge 100 as disclosed herein. Forexample, a blended bowl or structure may eliminate the need for areactive/functionalized silica 120 (e.g., silica 120 contained withinthe porous bowl 130); consequently at least some equipment (e.g.,dispensing equipment for the silica 120) may be eliminated or removedfrom the production line. Furthermore, a production line for producingvarious embodiments of the sample capture cartridge 100 disclosed hereinmay, for example, include a cartridge desiccant canister preparationstation and a clamping station. Such a cartridge desiccant canister 140preparation station may include a dispensing mechanism to consistentlydispense a volume of desiccant 150 into the porous bowl 130 and aseparate clamping station to append the cartridge lens cap 110 to thecartridge desiccant canister 140. A secondary clamping station may beused to mechanically couple the blended bowl with the cartridge lens cap110 (e.g., to the underside of the lens cap window 112) and subsequentlycouple the packed cartridge lens cap 110 (e.g., the cartridge lens cap110 containing the blended bowl) to the cartridge desiccant canister 140(which may be already pack with desiccant 150, absorbent pads, and/or acartridge desiccant retainer 160). Such simplification of the productionline may advantageously facilitate mass production of sample capturecartridges 100.

A blended bowl or structure, as disclosed herein, may confer additionalpotential benefits on a sample capture cartridge 100. For example ablended bowl may serve to reduce airflow resistance. In someembodiments, a blended bowl reduces airflow resistance by comparison toa porous bowl 130 containing a quantity of silica 120 more than about4%. In some embodiments, a blended bowl reduces airflow resistance bymore than about 1%, more than about 2%, more than about 3%, more thanabout 4%, more than about 5%, more than about 6%, more than about 7%,more than about 8%, more than about 9%, more than about 10%, more thanabout 12.5%, more than about 15%, more than about 17.5%, more than about20%, or any other reduction in airflow resistance that may beneficiallyfacilitate sample collection and analysis as disclosed herein.

In some embodiments, a blended bowl or structure facilitates analysis ofthe change resulting from interaction between thefunctionalized/reactive particles and the analyte of interest. Forexample, the blended bowl or structure may be placed directly under thelens cap window 112, thereby reducing the distance between any analysissystem (e.g., a photoanalysis system) and the collected analyte ofinterest. For example, the blended bowl prevents any movement of loosesilica 120 contained within the bowl (e.g., silica 120 contained withinthe porous bowl 130). As no silica 120 may move within the porous bowl130, turbulent mixing of the fluid sample with the silica 120 may beless critical. Additionally, when a blended bowl is used, movement ofthe sample capture cartridge 100 between sample collection and sampleanalysis may be less important (e.g., movement will, generally, notalter the position of the reactive/functionalized particles). As such,colorimetric changes may be analyzed more accurately when using ablended bowl.

In some embodiments, two separate disks, bowls, pucks, or other solidstructures may be created and incorporated into the cartridge, one whichcontains the reactive material, and one which contains a desiccant. Forexample, a reactive disc or puck may be created as described above(e.g., by blending functionalized silica or other particles with resinparticles), and a non-reactive desiccant disk or puck may be created byblending desiccant particles with resin particles using substantiallythe same process. These two solid, porous structures, each of which mayhave a cylindrical or puck-like configuration, may then be incorporatedinto the cartridge, with the desiccant structure positioned upstreamfrom the reactive structure in the breath flow path (to remove moisturefrom the breath sample before it reaches the reactive structure). Thetwo structures may optionally be fused or molded together to create asingle porous piece (which may have a cylindrical configuration) thatcontains a desiccant layer and a reactive layer, in which case thismulti-layer piece may be inserted into the cartridge with the desiccantlayer positioned upstream from the reactive layer.

Mechanical Sample Collection Whistle

FIGS. 8A-8B illustrate an embodiment of a sample capture cartridge 100,disclosed herein, being placed (e.g., snapped into) in an embodiment ofa sample collection whistle 200 (e.g., a device for collecting a sample,a reusable handheld analyte sample collection device, an analytecollector, a handheld breath collector, etc.) prior to collection of asample. While the sample collection whistle 200 is discussed inadditional detail herein, FIG. 8A shows the sample capture cartridge 100being loaded into the sample collection whistle 200 from a front-topthree-quarters view. In much the same way, FIG. 8B shows the samplecapture cartridge 100 being loaded into the sample collection whistle200 from a rear-top three-quarters view.

FIGS. 9A-9B illustrate an embodiment of a sample capture cartridge 100,disclosed herein, after being placed (e.g., snapped into) an embodimentof a sample collection whistle 200 (as shown in FIGS. 9A-9B, a samplemay or may not have already been collected).

FIGS. 8C-8F illustrate the sample collection whistle 200 of FIGS. 8A-8B,prior to loading of a sample capture cartridge 100. FIG. 8C shows thesample collection whistle 200 from the top. FIG. 8D shows the samplecollection whistle 200 from the side (e.g., the left side). FIG. 8Eshows the sample collection whistle 200 from the rear. FIG. 8F shows thesample collection whistle 200 from the front. As can be seen, the samplecollection whistle 200 generally has three main body pieces, including awhistle mouthpiece 210, a whistle core 220, and a whistle back 240. Someembodiments of the sample collection whistles disclosed herein do notinclude any sensors or other electronics. For example, the samplecollection whistles may not include any sensors or other electronics foranalyzing a sample collection cartridge or other sample collectionmodule to measure or analyze the concentration of an analyte.

Some embodiments of the sample collection whistles disclosed herein areportable, small, or hand-held devices. In some embodiments, the samplecollection whistle is less than about 10 cm long. In some embodiments,the sample collection whistle is shorter than about 20 cm, shorter thanabout 19.5 cm, shorter than about 19 cm, shorter than about 18.5 cm,shorter than about 18 cm, shorter than about 17.5 cm, shorter than about17 cm, shorter than about 16.5 cm, shorter than about 16 cm, shorterthan about 15.5 cm, shorter than about 15 cm, shorter than about 14.5cm, shorter than about 14 cm, shorter than about 13.5 cm, shorter thanabout 13 cm, shorter than about 12.5 cm, shorter than about 12 cm,shorter than about 11.5 cm, shorter than about 11 cm, shorter than about10.5 cm, shorter than about 10 cm, shorter than about 9.5 cm, shorterthan about 9 cm, shorter than about 8.5 cm, shorter than about 8 cm,shorter than about 7.5 cm, shorter than about 7 cm, shorter than about6.5 cm, shorter than about 6 cm, shorter than about 5.5 cm, shorter thanabout 5 cm, shorter than about 4.5 cm, shorter than about 4 cm, shorterthan about 3.5 cm, shorter than about 3 cm, shorter than about 2.5 cm,or shorter than about 2 cm. In some embodiments, the sample collectionwhistle weighs less than about 300 grams, less than about 280 grams,less than about 260 grams, less than about 240 grams, less than about220 grams, less than about 200 grams, less than about 180 grams, lessthan about 160 grams, less than about 140 grams, less than about 120grams, less than about 100 grams, less than about 80 grams, less thanabout 60 grams, or less than about 40 grams.

In some embodiments, the sample collection whistle 200 includes awhistle sample inlet 212. A whistle sample inlet 212 may be seen clearlyin FIG. 8F. As discussed in additional detail herein, when a sample isbeing taken, the fluid sample (e.g., breath) is inserted (e.g., blown)into the sample collection whistle 200 through the whistle sample inlet212 of the whistle mouthpiece 210 for collection by the sample capturecartridge 100.

In some embodiments, the sample collection whistle 200 (or any othersample collection whistle disclosed herein) is a hand-held collectiondevice, e.g., it may easily fit in and be used while in a user's hand.In some embodiments, the sample collection whistle 200 is about 3 incheslong. In some embodiments, the sample collection whistle 200 is betweenabout 1-6 inches long, between about 1.5-5.5 inches long, between about2-5 inches long, between about 2.5-4.5 inches long, between about 3-4inches long, or any other length that advantageously accepts and holds asample capture cartridge 100 as disclosed herein. In some embodiments,the sample collection whistle 200 is about 2.5 inches wide. In someembodiments, the sample collection whistle 200 is between about 1-5inches wide, between about 1.5-4.5 inches wide, between about 2-4 incheswide, between about 2.5-3.5 inches wide, about 3 inches wide, or anyother width that advantageously accepts and holds a sample capturecartridge 100 as disclosed herein. In some embodiments, the samplecollection whistle 200 is about 1 inch thick. In some embodiments, thesample collection whistle 200 is between about 0.25-3 inches thick,between about 0.5-2.75 inches thick, between about 0.75-2.5 inchesthick, between about 1-2.25 inches thick, between about 1.25-2 inchesthick, between about 1.5-1.75 inches thick, or any other thickness thatadvantageously accepts and holds a sample capture cartridge 100 asdisclosed herein.

In some embodiments, the sample collection whistle 200 is a purelymechanical device that contains no electrical components. For example,the sample collection whistle 200 may not contain any circuitry,sensors, etc. for analyzing a sample capture cartridge 100, a sample oranalyte of interest contained within a sample capture cartridge 100 orfor otherwise measuring any aspect of a sample. In some embodiments, thesample collection whistle 200 may include various electrical components,sensors, processors, actuators, circuitry, etc. In some embodiments, thesample collection whistle 200 may include electronics (sensors, etc.)for controlling a state of an aspect of the sample collection whistle200 (e.g., a valve or other element, such as the whistle button 250,that may control, partially or fully, or influence flow of a fluidsample through a sample collection cartridge (e.g., during exhalation),but lacks circuitry for analyzing the sample collection cartridge orotherwise measuring a concentration of the analyte of interest. In someembodiments, the sample collection whistle 200 contains variouselectrical components including, without limitation, various sensors foranalyzing a sample capture cartridge 100 or a sample or analyte ofinterest contained within or associated with a sample capture cartridge100. For example, the sample collection whistle 200 may contain variousprocessors and circuitry that automatically segment a sample. Forexample the sample collection whistle 200 may contain various sensors(e.g., optical sensors, or otherwise) that analyze the silica 120 (orblended bowl) contained beneath the cartridge lens cap 110 of the samplecapture cartridge 100.

In some embodiments, the whistle core 220 includes a cartridge insertionwindow 224 and a cartridge ejection window 222. Generally, the cartridgeinsertion window 224 will have dimensions (e.g., a height and a width)that allow insertion of a sample capture cartridge 100 through thecartridge insertion window 224 and into the body of the whistle core 220of the sample collection whistle 200. The cartridge ejection window 222may have dimensions that do not allow passage of a sample capturecartridge 100 through the cartridge ejection window 222. In someembodiments, the cartridge ejection window 222 is used to facilitateejection of a sample capture cartridge 100 after sample collection hasbeen completed. For example, after sample collection, a user may insertat least a portion of their finger or at least a portion of a tool intothe cartridge ejection window 222 to push the sample capture cartridge100 out of the cartridge insertion window 224. FIG. 8D shows theplacement of a cartridge insertion window 224 on the top of the whistlecore 220 and the cartridge ejection window 222 on the bottom of thewhistle core 220. Alternatively or in addition to the cartridge ejectionwindow 222, the whistle core 220 may include a sample capture cartridge100 ejection button that may be pressed to more conveniently eject thesample capture cartridge 100 from within the whistle core 220 of thesample collection whistle 200.

The whistle back 240 may include a whistle button 250. In someembodiments, the whistle button 250 is configured to move the samplecapture cartridge 100 within the whistle core 220. In some embodiments,the whistle button 250 is configured to move the sample capturecartridge 100 anteriorly in the whistle core 220 (e.g., towards thewhistle sample inlet 212 of the whistle mouthpiece 210). In someembodiments, the whistle button 250 is configured to move the samplecapture cartridge 100 posteriorly in the whistle core 220 of the samplecollection whistle 200 (e.g., away from the whistle sample inlet 212 ofthe whistle mouthpiece 210). In still other embodiments, the whistlebutton 250 is configured to move the sample capture cartridge 100 bothanteriorly (e.g., towards the whistle sample inlet 212 of the whistlemouthpiece 210) and posteriorly (e.g., away from the whistle sampleinlet 212 of the whistle mouthpiece 210) in the whistle core 220 of thesample collection whistle 200. Various embodiments of whistle button 250are disclosed herein.

FIGS. 9C-9F illustrate the sample collection whistle 200 shown in FIGS.8C-8F following insertion of a sample capture cartridge 100. FIG. 9C-9Fillustrate the sample collection whistle 200 after insertion of thesample capture cartridge 100 from the same angles as the samplecollection whistle 200 shown in FIGS. 8C-8F.

With reference to FIG. 9C, it can be seen that the cavity containing thesample capture cartridge 100 (e.g., after the sample capture cartridge100 was placed in through the cartridge insertion window 224) may havedimensions, e.g., height, width, and/or depth, slightly larger than thesample capture cartridge 100. In some embodiments, at least one of theheight, width, or depth, is larger than the corresponding dimension ofthe sample capture cartridge 100 by at least about 101%, at least about102%, at least about 103%, at least about 104%, at least about 105%, atleast about 106%, at least about 107%, at least about 108%, at leastabout 109%, at least about 110%, at least about lens cap window 112.5%,at least about 115%, at least about 117.5%, at least about 120%, or anyother increase in size that advantageously facilitations acceptance andtemporary retention of a sample capture cartridge 100 as disclosedherein.

With reference to FIG. 9F, the cartridge desiccant retainer 160 of thesample capture cartridge 100 may be seen through the whistle sampleinlet 212 of the whistle mouthpiece 210 of the sample collection whistle200.

After insertion of a sample capture cartridge 100 through the cartridgeinsertion window 224 and into the whistle core 220, some space may existbetween the sample capture cartridge 100 and any surface of the samplecollection whistle 200. As such, a fluid inserted through the whistlesample inlet 212 of the whistle mouthpiece 210 may escape from thesample collection whistle 200, e.g., from the gap between the samplecapture cartridge 100 and the sample collection whistle 200. This is dueto the principle of fluids following a path of least resistance. Evenwhen the sample capture cartridge 100 is inserted more proximally in thesample collection whistle 200 (e.g., closer to the whistle sample inlet212), the pressure of the fluid being inserted through the whistlesample inlet 212 may push the sample capture cartridge 100 distally inthe whistle core 220 (e.g., towards the whistle back 240), therebyincreasing the gap between the sample capture cartridge 100 and thewhistle mouthpiece 210 and creating a space through which the fluidsample may escape.

The whistle button 250 may be actuated to force the sample capturecartridge 100 proximally within the whistle core 220 such that the baseof the cartridge desiccant canister 140 of the sample capture cartridge100 may seal or substantially seal against a surface or portion of thesample collection whistle 200 (e.g., a surface of the whistle mouthpiece210). When the base of the cartridge desiccant canister 140 is forcedagainst the surface, the gap between the sample capture cartridge 100and the whistle core 220 may be substantially eliminated, therebychanging the path of least resistance to be through the sample capturecartridge 100, e.g., through the whistle sample inlet 212, and into thecartridge desiccant canister 140, through the cartridge desiccantretainer 160, through the desiccant 150, through the canister cavity144, and through the porous bowl 130 and silica 120 (or the blendedbowl) and out of lens cap vents 114 of the cartridge lens cap 110.

When the whistle button 250 is not being actuated, e.g., pushed, the gapbetween the sample capture cartridge 100 and the whistle core 220 mayallow a substantial portion of the fluid sample to escape withoutpassing through the sample capture cartridge 100. In some embodiments,when the whistle button 250 is not actuated, the percentage of the fluidsample that escapes the sample collection whistle 200 without passingthrough the sample capture cartridge 100 is at least about 50%, at leastabout 60%, at least about 70%, at least about 80%, at least about 85%,at least about 90%, at least about 91%, at least about 92%, at leastabout 93%, at least about 94%, at least about 95%, at least about 96%,at least about 97%, at least about 98%, or at least about 99%.

When the whistle button 250 is being actuated, e.g., pushed, the gapbetween the sample capture cartridge 100 and the whistle core 220 isclosed and a substantial portion of the fluid sample is not permitted toescape and is forced through the sample capture cartridge 100. In someembodiments, when the whistle button 250 is actuated, the percentage ofthe fluid sample that passes through the sample capture cartridge 100 isat least about 50%, at least about 60%, at least about 70%, at leastabout 80%, at least about 85%, at least about 90%, at least about 91%,at least about 92%, at least about 93%, at least about 94%, at leastabout 95%, at least about 96%, at least about 97%, at least about 98%,or at least about 99%.

With reference to FIG. 10D, the whistle mouthpiece 210 may include acartridge sealing grommet 214. For example the whistle mouthpiece 210may hold a cartridge sealing grommet 214 against which the samplecapture cartridge 100 is pushes when the whistle button 250 is actuated.In some embodiments, the cartridge sealing grommet 214 is a lowerdurometer material, such as a rubber, that is configured toadvantageously form a tight seal with the cartridge desiccant canister140 of the sample capture cartridge 100 (e.g., the cartridge sealinggrommet 214 has a diameter that is larger than the diameter of thecartridge desiccant canister 140 of the sample capture cartridge 100such that the entire perimeter of the lower surface or ring of thecartridge desiccant canister 140 may be effectively pressed into thecartridge sealing grommet 214). In such embodiments, when the whistlebutton 250 is actuated, the sample capture cartridge 100 is movedproximally in the whistle core 220 toward the whistle mouthpiece 210such that the cartridge desiccant canister 140 of the sample capturecartridge 100 contacts and seals against the cartridge sealing grommet214 of the whistle mouthpiece 210. Therefore, the fluid sample flowsinto the whistle sample inlet 212, through the cartridge sealing grommet214 (e.g., through a central aperture of the cartridge sealing grommet214) and into the various internal portions of the sample capturecartridge 100 and out of the lens cap vents 114 of the cartridge lenscap 110. The cartridge sealing grommet 214 of the whistle mouthpiece 210may advantageously increase the percentage of the fluid sample thatpasses through the sample capture cartridge 100 (and reduce thepercentage of the fluid sample that escapes through gaps ordiscontinuities in the system). For example, when the cartridge sealinggrommet 214 is included in the whistle mouthpiece 210, when the whistlebutton 250 is actuated, the percentage of the fluid sample that passesthrough the sample capture cartridge 100 is at least about 90%, at leastabout 91%, at least about 92%, at least about 93%, at least about 94%,at least about 95%, at least about 96%, at least about 97%, at leastabout 98%, or at least about 99%.

The ability of the whistle button 250 of the sample collection whistle200 to dictate how much of the fluid sample escapes the sample capturecartridge 100 and/or is forced through the sample capture cartridge 100allows segmentation of a fluid sample. For example, a portion of a fluidsample (e.g., an initial portion of the fluid sample) may intentionallybe vented by the sample collection whistle 200. Then, upon actuation ofthe whistle button 250, a later portion of the fluid sample may beforced through the sample capture cartridge 100 and an analyte ofinterest from that later portion of the fluid sample collected by thesample capture cartridge 100. Such sample segmentation may beadvantageously applied to breath samples to separate a breath, e.g., toseparate tidal volume from alveolar air. Tidal volume is the portion ofa breath that is displaced in normal inhalations and exhalations when noextra effort is applied (e.g., sitting still, at rest, breathingnormally without extra depth). Under normal circumstances, the tidalvolume comprises a portion of dead-space, mixed air (including a mixtureof dead-space and alveolar air), and alveolar air. The dead-space is airfrom at least one of the trachea, nasal cavity, and mouth. The mixed airincludes some breath sourced from the deeper regions of the lung,including, for example, the alveoli, but it also contains some breathsourced from the dead-space. The final segment, alveolar air, is sourcedsubstantially entirely from the deeper segments of the lungs, includingthe alveoli—this, third and final segment is generally appropriate foranalyzing as an alveolar breath sample. Therefore, the whistle button250 may be used to effectively separate a breath to collectsubstantially only alveolar air.

FIGS. 10A-10D illustrate various internal components of an embodiment ofa sample collection whistle 200. FIG. 10A illustrates a top-biased sideview of sample collection whistle 200. The sample collection whistle 200shown in FIG. 10A is the same as the sample collection whistle 200 shownin FIG. 8C, except that the whistle core 220 is removed, showing theinternal components covered by that portion. In addition to the whistlemouthpiece 210 (having a whistle sample inlet 212) and the cartridgesealing grommet 214 (having a whistle button 250), two whistle leaders230 each having a leader fin 232, and the whistle pusher 260 may beseen. The sample collection whistle 200 shown in FIG. 10B is the same asthe sample collection whistle 200 shown in FIG. 10A, except that thewhistle back 240 is removed and a sample capture cartridge 100 is shownbeing held by the whistle leaders 230. The sample collection whistle 200shown in FIG. 10C is the sample collection whistle 200 shown in FIG.10B, except from a rear angle. Finally, the sample collection whistle200 shown in FIG. 10D is a cross-sectional view of the sample collectionwhistle 200 shown in FIG. 10A, taken along line A-A, except that thewhistle back 240 has been removed for easier viewing.

The whistle leaders 230 and their respective leader fin 232 may be heldin sockets. On socket may be associated with or attached to (e.g.,coupled to, fixed to, or otherwise part of) the whistle back 240 and onesocket may be associated with or attached to (e.g., coupled to, fixedto, or otherwise part of) the whistle mouthpiece 210. The whistle leader230 may be pivotable within the sockets. Each of leader fin 232 servesas a spring to bias the whistle leader 230 inwards. As might be seenmost clearly from FIG. 10C, each leader fin 232 extend outwardly (e.g.,laterally out) from the rotational axis of the whistle leader 230 andtoward the inner wall of the sample collection whistle 200. Morespecifically, each leader fin 232 is configured to be in closeapproximation or in contact with an inner surface of the whistle core220. In this way, when the sample collection whistle 200 is assembled,the leader fins 232 constantly push or bias the whistle leaders 230inward. The whistle leaders 230 are dimensioned so that a sample capturecartridge 100 may be pushed between them (e.g., they may be shaped likeinverted “L”s). When a sample capture cartridge 100 is pushed betweenthe whistle leaders 230 the whistle leaders 230 push away from thecenter of the cartridge insertion window 224, against the leader fins232, thereby allowing the sample capture cartridge 100 to pass betweenthe whistle leaders 230. Once the sample capture cartridge 100 passesthe whistle leaders 230 (e.g., the widest diameter of the sample capturecartridge 100 passes past the top of the whistle leaders 230), or“snaps” into place, the leader fins 232 push the whistle leaders 230back out over the sample capture cartridge 100 to hold the samplecapture cartridge 100 in place within the whistle core 220. In this way,the sample capture cartridge 100 may be simply and easily held in placeduring use (e.g., axially aligned with the whistle sample inlet 212and/or the cartridge sealing grommet 214).

In much the same way, once a sample collection has been completed, thesample capture cartridge 100 may be pushed out of the whistle core 220by applying pressure to the sample capture cartridge 100 through thecartridge ejection window 222. Upward pressure on the sample capturecartridge 100 pushes the sample capture cartridge 100 up and against thewhistle leaders 230, which causes them to rotate outward, against thespring force of the leader fins 232. Upon application of sufficientpressure (which, in most cases may be relatively light) the spring forceof the leader fins 232 may be overcome and the sample capture cartridge100 may snap or pop past the whistle leaders 230 and out of the whistlecore 220 of the sample collection whistle 200.

As can be seen in FIGS. 10A and 10D, the whistle pusher 260 may be asubstantially cylindrical. The whistle pusher 260 may have alongitudinal axis. In some embodiments, the longitudinal axis of thewhistle pusher 260 may substantially align with the axis of thecartridge sealing grommet 214 (e.g., the opening through the cartridgesealing grommet 214). In some embodiments, the longitudinal axis of thewhistle pusher 260 may substantially align with the center of the samplecapture cartridge 100 (e.g., the longitudinal axis of the sample capturecartridge 100). In some embodiments, the whistle pusher 260 may bealigned with the center of the cartridge lens cap 110 of the samplecapture cartridge 100. In other words, the whistle pusher 260 may pushon the sample capture cartridge 100 substantially at or near the centerof the lens cap window 112 of the cartridge lens cap 110.

In some embodiments, the whistle pusher 260 has a substantiallycylindrical shape. In some embodiments, the whistle pusher 260 has adiameter of about 5-6 mm. In some embodiments, the whistle pusher 260has a diameter in the range of between about 2-35 mm, between about2.5-30 mm, between about 3-25 mm, between about 3.5-20 mm, between about4-15 mm, between about 4.5-10 mm, between about 5-8 mm, or any otherdiameter that advantageously facilitates moving a sample capturecartridge 100 proximally (e.g., towards the mouthpiece) in the samplecollection whistle 200. Of course, the whistle pusher 260 may have anyof a number of shapes other than cylindrical. For example, the whistlepusher 260 may be triangular, rectangular, pentagonal, or hexagonal.Indeed, any shape of whistle pusher 260 may be used that advantageouslyfacilitates moving a sample capture cartridge 100 proximally (e.g.,towards the mouthpiece) in the sample collection whistle 200.

In some embodiments, the whistle pusher 260 has a shape and/or a featureto protect the lens cap window 112 of the cartridge lens cap 110.Because some embodiments of the sample capture cartridge 100 opticallyanalyze a material change through the lens cap window 112 it may beadvantageous to protect the lens cap window 112 from scratches, marring,or any other damage that might change the transparency of the lens capwindow 112, whether locally or otherwise. In some embodiments, thewhistle pusher 260 terminates in a pad that protects the lens cap window112, e.g., prevents the lens cap window 112 from being scratched ormarred. Such a protective pad may be constructed out of felt, fibers,rubber, etc. The protective pad may be any material that has a lowerdurometer than the lens cap window 112 so that that it does not scratch,mar, or damage the lens cap window 112. In some embodiments, the whistlepusher 260 terminates in a cone or cylinder with an open center. Such acone or cylinder may be configured to push against the top of thecartridge lens cap 110 without touching the center of the cartridge lenscap 110, e.g., where the lens cap window 112 is located.

With continued reference to FIG. 10D, the whistle pusher 260 may includea pusher ramp 262 and the whistle button 250 may include a correspondingbutton ramp 252. When the whistle button 250 is depressed (e.g.,actuated), it travels into the sample collection whistle 200 in adirection that is substantially perpendicular to the longitudinal axisof the whistle pusher 260. As the whistle button 250 and the button ramp252 move down, into the sample collection whistle 200, the button ramp252 causes the pusher ramp 262 to slide along the interface between thebutton ramp 252 and the pusher ramp 262. As the pusher ramp 262 slides,the whistle pusher 260 is moved forward, e.g., proximally within thesample collection whistle 200. Of course, one of ordinary skill in theart will understand that the ramped interface that includes button ramp252 and pusher ramp 262 is merely one way of actuating whistle pusher260 to move a sample capture cartridge 100 (when in place) proximally inthe sample collection whistle 200.

Noisemaker Sample Collection Whistle

Some embodiments of the sample collection whistle 200 disclosed hereincontain various functionality to alert a user or a device monitoring thesample collection of one or more statuses of the sample collectionwhistle 200. For example, the sample collection whistle 200 may includefunctionality to facilitate segmentation of a fluid sample.

FIG. 11A shows an embodiment of a sample collection whistle 200 that isconfigured to make a noise when fluid passes through the samplecollection whistle 200. FIG. 11B shows the sample collection whistle 200of FIG. 11A from the front, and shows one embodiment of a noise makerthat may be included in the sample collection whistle 200. FIG. 11Cshows the embodiment of the noisemaker of FIG. 11B. As shown in FIG.11C, one possible noise maker includes a stationary vane 270 attached toa rotating vane 272 that rotates when a fluid is pushed through at asufficient rate. However, one of ordinary skill in the art will readilygrasp that many different types of noise makers may be used.

In some embodiments, the sample collection whistle 200 includes a noisemaker that makes a noise when fluid is pushed through (e.g., blownthrough) the whistle sample inlet 212 of the whistle mouthpiece 210 at asufficient rate, regardless of whether a sample capture cartridge 100 isin place or not. In some embodiments, the noise made by the noise makeris a tone or a whistle. In some embodiments, the sample collectionwhistle 200 includes a noise maker that: makes a first noise when fluidis pushed through the whistle sample inlet 212 of the whistle mouthpiece210 at a sufficient rate and a sample capture cartridge 100 is present,but the whistle button 250 is not actuated; and makes a second noisewhen fluid is pushed through the whistle sample inlet 212 of the whistlemouthpiece 210 at a sufficient rate and a sample capture cartridge 100is present and the whistle button 250 is actuated. In some embodiments,the sample collection whistle 200 includes a noise maker that: makes afirst noise when fluid is pushed through the whistle sample inlet 212 ofthe whistle mouthpiece 210 at a sufficient rate, but a sample capturecartridge 100 is not present; makes a second noise when fluid is pushedthrough the whistle sample inlet 212 of the whistle mouthpiece 210 at asufficient rate and a sample capture cartridge 100 is present, but thewhistle button 250 is not actuated; and makes a third noise when fluidis pushed through the whistle sample inlet 212 of the whistle mouthpiece210 at a sufficient rate and a sample capture cartridge 100 is presentand the whistle button 250 is actuated. In some embodiments, the samplecollection whistle 200 includes a noise maker that: makes a first noisewhen fluid is pushed through the whistle sample inlet 212 of the whistlemouthpiece 210 at a sufficient rate, but the whistle button 250 is notactuated; and makes both the first noise and a second noise (e.g., asecond noise different or distinct from the first noise) when fluid ispushed through the whistle sample inlet 212 of the whistle mouthpiece210 at a sufficient rate and a sample capture cartridge 100 is presentand the whistle button 250 is actuated.

In some embodiments, the sample capture cartridge 100 includes a noisemaker that makes a noise when fluid is pushed through (e.g., blownthrough) the sample capture cartridge 100 and out of the lens cap vent114 of the cartridge lens cap 110 at a sufficient rate. In someembodiments, the sample capture cartridge 100 includes a noise makerthat makes a first noise after the whistle button 250 of the samplecollection whistle 200 has been actuated (e.g., only after the whistlebutton 250 has been actuated may there be sufficient flow through thenoise maker to produce the first sound).

In some embodiments both the sample collection whistle 200 and thesample capture cartridge 100 include a noise maker. For example thesample collection whistle 200 may include a noise maker that makes afirst noise when fluid is pushed through the whistle sample inlet 212 ofthe whistle mouthpiece 210 at a sufficient rate (regardless of whether asample capture cartridge 100 is in place and/or whether a sample capturecartridge 100 is in place and the whistle button 250 is actuated). Thesample capture cartridge 100 may include a noise maker than makes asecond noise when fluid is pushed through the sample capture cartridge100 (e.g., into the cartridge desiccant canister 140 or out of the lenscap vents 114) at a sufficient rate. In such embodiments, a first noisemay be generated upon pushing a fluid through the whistle sample inlet212 of the whistle mouthpiece 210 at a sufficient rate, but the secondnoise (e.g., of the noise maker of the sample capture cartridge 100)will not be generated until the whistle button 250 is actuated (e.g., aseal is created between the sample capture cartridge 100 and thecartridge sealing grommet 214) such that sufficient fluid is forcedthrough the sample capture cartridge 100.

Embodiments of the sample collection whistle 200 and/or sample capturecartridge 100 that include one or more noisemakers may advantageouslyfacilitate simple sample segmentation. For example, a microphone, aprocessor and a software (e.g., a mobile phone having a microphone andan app) may be able to detect any of noises (e.g., sounds, tones, notes,etc.) discussed above (e.g., the first noise, second noise, and/or thirdnoise). The processor and software (e.g., sound analyzer) may thereforedetect any of a number of things, by analyzing the noise(s) produced bythe sample collection whistle 200 and/or sample capture cartridge 100.For example, the sound analyzer may be able to detect when a sample isbeing pushed through the sample collection whistle 200 at a ratesufficient to be an appropriate sample (e.g., it can detect thebeginning of sample flow) (e.g., when it detects a sound indicative ofthe sample flow). The sound analyzer may also be able to detect thepresence of a sample capture cartridge 100 (e.g., when it detects asound indicative of sample flow, but either a sound indicative of theabsence of the sample capture cartridge 100 or the absence of a soundindicative of the sample capture cartridge 100). The sound analyzer mayalso be able to detect when the whistle button 250 was actuated (e.g.,it may be able to detect a change in the sound or detect the addition ofanother sound).

In view of the above, a sound analyzer may be able to provide real-timesegmentation instructions to a user. For example, if a late segmentsample is desirable, the sound analyzer may start a time upon hearing asound indicative of the beginning of sample flow. After a sufficienttime has passed such that the late segment of the sample has beenreached, the sound analyzer may signal the user to actuate the whistlebutton 250 to engage the sample capture cartridge 100 with the samplestream and capture at least part of the late segment sample. The soundanalyzer may be able to determine the success of the sample collectionbased on the change of the sound (e.g., pitch, volume, and/or any newsounds) and the duration of such changed sound. In some embodiments, thesound analyzer may be attached to an automatic actuator that may replacethe whistle button 250. In such embodiments, the sound analyzer mayautomatically segment a sample based on any of a number of criteria,which may be pre-programmed into the sound analyzer.

Electronic Sample Collection Whistle

FIGS. 26A-26B illustrate various views of an embodiment of a samplecapture cartridge 100, as disclosed herein, installed or placed in(e.g., snapped into) an embodiment of sample collection whistle 2600.While the sample collection whistle 2600 is discussed in additionaldetail herein, FIG. 26A shows sample capture cartridge 100 loaded in thesample collection whistle 2600 from a top-front biased three-quartersview. In much the same way, FIG. 26B shows the sample capture cartridge100 loaded in the sample collection whistle 2600 from a top-rear biasedthree-quarters view.

FIGS. 26C-26E show the sample collection whistle 2600 of FIGS. 26A-26Bwith one or more external components, such as a plastic housing,removed, so that the various internal components of the samplecollection whistle 2600 may be better seen. FIG. 26C shows a front-topbiased three quarters view of the internal components of the samplecollection whistle 2600, e.g., with various external housing componentsremoved. FIG. 26D-26E show a rear-top biased three quarters view of theinternal components of the sample collection whistle 2600, e.g., withvarious external housing components removed.

One or more components of the sample collection whistle 2600 of FIGS.26A-26E may be similar in structure and/or function to the samplecollection whistle 200 of FIGS. 8A-10D. For example: the whistle sampleinlet 2612 may correspond to the whistle sample inlet 212; the whistlemouthpiece 2610 may correspond to the whistle mouthpiece 210, thecartridge insertion window 2624 may correspond to the cartridgeinsertion window 224; the whistle back 2640 may correspond to thewhistle back 240; and the cartridge sealing grommet 2614 may correspondto the cartridge sealing grommet 214. While some components may besimilar, or even identical between the sample collection whistle 2600and the sample collection whistle 200, none are required to be similar,substantially similar, or identical.

As shown in FIG. 26A, the sample collection whistle 2600 has a whistlebody 2620 with a cartridge insertion window 2624 at or near its middle.The cartridge insertion window 2624 may be at any location convenientfor a user to insert and remove a sample capture cartridge 100 fromwithin the cartridge insertion window 2624. At the front of the samplecollection whistle 2600, best seen in FIG. 26A, is a whistle mouthpiece2610 having a whistle sample inlet 2612. As best seen in FIG. 26B, thesample collection whistle 2600 includes a whistle back 2640 at its rear.The rear of the sample collection whistle 2600 may also include abattery cover 2642 that may be opened and closed by a user to removeand/or replace batteries into the whistle body 2620.

In some embodiments, the sample collection whistle 2600 includes twoflow paths (e.g., most relevant when a sample capture cartridge 100 isin place within the sample collection whistle 2600), a sample collectionflow path and an exhaust or venting flow path. The sample collectionflow path begins at the whistle mouthpiece 2610, where it passes intothe whistle sample inlet 2612, through the cartridge sealing grommet2614, through the sample capture cartridge 100, and out of the lens capvents 114 of the sample capture cartridge 100 to the atmosphere. Theexhaust or venting flow path begins at the whistle mouthpiece 2610,where it passes into the whistle sample inlet 2612, then through theexhaust vent 2685 and out to the atmosphere. Flow of gases through thesetwo flow paths may be dependent or modulated based on the restriction toflow of the various flow paths.

In some embodiments, the restriction to flow of the exhaust or ventingflow path has an opened configuration and a closed configuration. Insome embodiments, the exhaust or venting flow path may be opened andclosed in many different ways. As shown in FIGS. 26C-26D, the samplecollection whistle 2600 includes a solenoid 2682 that drives a stopshaft 2684, e.g., linearly drives. The solenoid 2682 is configured todrive stop shaft 2684 to extend it into the exhaust vent 2685 to closethe exhaust vent 2685, thereby blocking the exhaust or venting flowpath. In the same way, the solenoid 2682 is configured to drive stopshaft 2684 to withdraw it from the exhaust vent 2685 to open the exhaustvent 2685, thereby opening the exhaust or venting flow path. The stopshaft 2684 may mate, e.g., closely mate or sealingly mate, with theexhaust vent 2685 such that when the stop shaft 2684 is within theexhaust vent 2685, the flow through the exhaust or venting flow path isdecreased by at least about 80%, at least about 85%, at least about87.5%, at least about 90%, at least about 92.5%, at least about 95%, atleast about 97.5%, or at least about 99%. FIG. 26D shows the stop shaft2684 backed out of the exhaust vent 2685, leaving the exhaust or ventingflow path open.

When the exhaust or venting flow path is open and a sample capturecartridge 100 is installed in the sample collection flow path, thesample capture cartridge 100 provides a substantial amount of flowresistance, such that the resistance to flow of the exhaust or ventingflow path is less, e.g., significantly less, than the resistance to flowof the sample collection flow path. In this case, the amount of flowpassing through the exhaust or venting flow path and to the atmosphereis at least about 80%, at least about 85%, at least about 87.5%, atleast about 90%, at least about 92.5%, at least about 95%, at leastabout 97.5%, or at least about 99%. FIG. 26E shows the stop shaft 2684extending into the exhaust vent 2685, blocking, closing, or sealing theexhaust or venting flow path.

When the exhaust or venting flow path is closed and a sample capturecartridge 100 is installed in the sample collection flow path, the flowis substantially blocked from passing through the exhaust or ventingflow path and most of the flow is directed or forced through the samplecapture cartridge 100 (less any losses due to imperfect fittings) as auser exhales or blows into the whistle. In this case, the amount of flowpassing through the sample collection flow path and through the samplecapture cartridge 100 is at least about 80%, at least about 85%, atleast about 87.5%, at least about 90%, at least about 92.5%, at leastabout 95%, at least about 97.5%, or at least about 99%.

In some embodiments, the sample capture cartridge 100 is held securelyin the sample collection whistle 2600 (e.g., to create a sealed samplecollection flow path) by a ball 2681 (e.g., a plastic ball) and spring2680 that push the sample capture cartridge 100 anteriorly against thecartridge sealing grommet 2614. Any type of spring or holding mechanismmay be used. In some embodiments, in this or any other whistle disclosedherein, the mechanism used to retain the sample capture cartridge 100within the sample collection whistle minimizes contact with or does notcontact the lens cap window 112 so as to advantageously prevent damageto the window that may cause noise or artifacts in subsequent reading ofthe sample.

The solenoid 2682 may be run by battery 2644, which may be arechargeable or replaceable battery 2644, e.g., removable by opening thebattery cover 2642. Additionally, the sample collection whistle 2600 mayinclude various components, e.g., electrical components, necessary torun the solenoid and or other electrical components of the samplecollection whistle 2600. For example, the sample collection whistle 2600may include a PCB.

The sample collection whistle 2600 may be used to segment breath samplesso that deep-lung samples may be selectively collected. In operation, auser may insert a sample capture cartridge 100, e.g., a disposablereplaceable cartridge, into the sample collection whistle 2600 throughthe cartridge insertion window 2624. The sample capture cartridge 100 isheld in the sample collection whistle 2600 by the spring 2680 and theball 2681.

The sample collection whistle 2600 may be turned on in any of a numberof ways. In some embodiments, the sample collection whistle 2600 isturned on when the user presses an “on/off” button. In some embodiments,the sample collection whistle 2600 is turned on when the user beginsblowing into the whistle sample inlet 2612 of the sample collectionwhistle 2600, e.g., the sample collection whistle 2600 may have a flowsensor that automatically turns the device on when sufficient flow issensed. In some embodiments, the sample collection whistle 2600 isturned on when the user interacts with an application on a mobiledevice, such as a smart phone (e.g., the sample collection whistle 2600may have wired or wireless connectivity such that it may connect to andcommunicate with another device).

To collect a deep-lung breath sample, the sample collection whistle 2600selectively vents an initial portion of the user's breath. To do this,the sample collection whistle 2600 keeps the exhaust or venting flowpath open for a set portion of the user's breath (as discussed above,the exhaust or venting flow path is open when the solenoid 2682 hasbacked the stop shaft 2684 out of the exhaust vent 2685). When theexhaust or venting flow path is open, a majority of the breath flowbeing generated by the user will be exhausted to the atmosphere, ratherthan passing through and being collected by the sample capture cartridge100. The sample collection whistle 2600 may segment the user's breathbased on any of a number of factors, such as time, pressure, flow rate,flow volume, or any of a number of other criteria that may be patientspecific and programmed into the sample collection whistle 2600(alternatively, the sample collection whistle 2600 may communicate withand receive segmenting instructions from the aforementioned mobiledevice). In addition, the device may detect the beginning of exhalationand use that time point as the start, e.g., starting point, for one ormore measurements, such as flow, time, volume, etc.

Once the sample collection whistle 2600 has determined or beeninstructed that the desired breath segment has been reached, whether bytime volume or any other metric, a programmed controller controls thesolenoid 2682 and causes it to move the stop shaft 2684 into engagementwith the exhaust vent 2685 to close the exhaust or venting flow path. Asdiscussed herein, when the venting or exhaust flow path is closed, gasesentering the sample collection whistle 2600 will be forced through thecartridge sealing grommet 2614 and through the sample capture cartridge100 to be collected as a sample.

Once the flow path has changed, e.g., the solenoid 2682 has closed theexhaust flow path by inserting the stop shaft 2684 into the exhaust vent2685, the user may continue to exhale for a time during which the samplecapture cartridge 100 collects a sample of the user's breath.

In some embodiments, the user merely continues exhaling until he or sheis no longer able to exhale (e.g., has no more breath). In someembodiments, the sample collection whistle 2600 is configured toinstruct the user when to stop exhaling. In some embodiments, the samplecollection whistle 2600 instructs the user to stop exhaling based on theamount of time the user has exhaled. In some embodiments, the samplecollection whistle 2600 instructs the user to stop exhaling based on thevolume of air that has passed through the sample collection flow path.In some embodiments, the sample collection whistle 2600 instructs theuser to stop exhaling based on changes in flow rate of the air passingthrough the sample collection flow path. In some embodiments, the samplecollection whistle 2600 instructs the user to stop exhaling based onfeedback received from the mobile device. The task of informing the userwhen to stop exhaling may be performed by a mobile app based on awireless signal generated by the whistle, e.g., a component of thewhistle.

The sample collection whistle 2600 may provide a signal to the userindicating that he or she should stop exhaling. For example, the samplecollection whistle 2600 may include one or more LEDs that signal theuser to stop exhaling, e.g., by illuminating, flashing, etc. Inaddition, or instead of LEDs, the sample collection whistle 2600 mayprovide an auditory signal, such as beeps, clicks, tones, etc., thatsignals the user to stop exhaling. Such visual or auditory signals mayalso be used to instruct the user to begin blowing or exhaling into the2600.

The sample collection whistle 2600 may be programmed with longer orshorter times for exhausting and sample collection based on usercharacteristic(s). For example, in some embodiments, the user may inputone or more of his or her physical characteristics, e.g., age, gender,weight, health, etc., into the sample collection whistle 2600. In someembodiments, the user may input one or more of his or her physicalcharacteristics, e.g., age, gender, weight, etc., into a mobile devicewith which the sample collection whistle 2600 communicates. In someembodiments, the exhausting stage can be lengthened in response to oneor more of the user's physical characteristics. In some embodiments, theexhausting stage can be shortened in response to one or more of theuser's physical characteristics. In some embodiments, the samplecollection stage can be lengthened in response to one or more of theuser's physical characteristics. In some embodiments, the samplecollection stage can be shortened in response to one or more of theuser's physical characteristics.

In some embodiments, the sample collection whistle 2600 includes memorysuch that it can store one or more data regarding the user, testingconditions, one or more tests, etc.

FIGS. 27A-27B illustrate an embodiment of a rotary valve 2700 that maybe used in connection with one or more sample collection whistlesdisclosed herein, e.g., sample collection whistle 2600 (in place of thesolenoid 2682 and stop shaft 2684). FIG. 27A shows the rotary valve 2700in an open, or flow permitting configuration. FIG. 27B shows the rotaryvalve 2700 in a substantially closed, or flow blocking configuration.

The rotary valve 2700 includes a rotary valve inner sleeve 2712 nestedinside a rotary valve outer sleeve 2710. Each of the rotary valve outersleeve 2710 and rotary valve inner sleeve 2712 includes an outlet 2742.Additionally, the rotary valve inner sleeve 2712 has an inlet 2740. Therotary valve inner sleeve 2712 is configured to rotate within the rotaryvalve outer sleeve 2710 (or the rotary valve outer sleeve 2710 isconfigured to rotate about the rotary valve inner sleeve 2712). Rotationof the rotary valve inner sleeve 2712 with respect to the rotary valveouter sleeve 2710 may move the outlet 2742 of the rotary valve outersleeve 2710 into and out of alignment with the outlet 2742 of the rotaryvalve inner sleeve 2712. When the outlet 2742 of the rotary valve outersleeve 2710 completely overlaps with the outlet 2742 of the rotary valveouter sleeve 2710, the rotary valve 2700 is open or permits flow (shownin FIG. 27A). When the outlet 2742 of the rotary valve outer sleeve 2710is not aligned or overlapping at all with the outlet 2742 of the rotaryvalve inner sleeve 2712, the rotary valve 2700 is closed or blocks flow.The rotary valve 2700 may block more or less flow based on how muchoverlap exists between the outlet 2742 of the rotary valve outer sleeve2710 and the outlet 2742 of the rotary valve inner sleeve 2712. FIG. 27Bshows the outlet 2742 of the rotary valve outer sleeve 2710 overlappingonly very slightly with the outlet 2742 of the rotary valve inner sleeve2712: in this case, little flow would be permitted to pass through therotary valve 2700.

Each of the rotary valve outer sleeve 2710 and the rotary valve innersleeve 2712 may be constructed out of plastic. The outlet 2742 of therotary valve outer sleeve 2710 may be substantially perpendicular to anaxis of the rotary valve outer sleeve 2710 and the 1712, e.g., alongitudinal axis of the rotary valve outer sleeve 2710 and the rotaryvalve inner sleeve 2712 (which may lie on the same axis).

One of the rotary valve outer sleeve 2710 and the rotary valve innersleeve 2712 is fixedly attached to, e.g., press-fitted, onto the driveshaft 2720, which may be connected to a slow-turning, high-torque,micro-motor. In some embodiments, the press fit is tight enough that themotor can turn one of the rotary valve outer sleeve 2710 and the rotaryvalve inner sleeve 2712 with respect to the other of the rotary valveouter sleeve 2710 and the rotary valve inner sleeve 2712 (e.g., so thatthe drive shaft 2720 may turn the rotary valve inner sleeve 2712 withrespect to the rotary valve outer sleeve 2710).

One or both of the rotary valve inner sleeve 2712 and the rotary valveouter sleeve 2710 may include a turn-stop 2730. The turn-stop 2730 mayserve to stop rotation of the rotary valve inner sleeve 2712 withrespect to the rotary valve outer sleeve 2710. In some embodiments, whenthe turn-stop 2730 prevents further turning, the press-fit between thedrive shaft 2720 and the rotary valve inner sleeve 2712 is overcome andthe motor is allowed to turn the drive shaft 2720 freely inside therotary valve inner sleeve 2712. This can advantageously allow forimperfect run times of the electronic motor and may prevent the need forany form of sensor feedback, e.g., sensor feedback to the PCB. The motorcan be run for an approximate, e.g., non-exact, time to open or closethe valve. In some embodiments, the rotary motor is more exact and aturn-stop 2730 is not necessary. When the rotary motor is more precise,the flow rate allowed through the rotary valve 2700 may be modulatedbased on the overlap between the outlet 2742 of the rotary valve outersleeve 2710 and the outlet 2742 of the rotary valve inner sleeve 2712.

Hybrid Mechanical and Electronic Sample Collection Whistle

FIGS. 28A-28C, 29A-29C, and 30A-30C illustrate an embodiment of a samplecollection whistle 2800 that may be used in conjunction with a samplecapture cartridge 100, as disclosed herein, to collect and/or segment asample. FIGS. 28A-28C show various view of the sample collection whistle2800 without a sample capture cartridge 100 loaded into the samplecollection whistle 2800. FIGS. 29A-29C show the same views as FIGS.28A-29C, except with a sample capture cartridge 100 loaded into thesample collection whistle 2800, such as it might look while taking asample. FIGS. 30A-30C show various cross-sectional views of the samplecollection whistle 2800 shown in FIGS. 28A-28C and 29A-29C.

One or more components of the sample collection whistle 2800 of FIGS.28A-28C, 29A-29C, and 30A-30C may be similar in structure and/orfunction to the sample collection whistle 200 of FIGS. 8A-10D and/or thesample collection whistle 2600 of FIGS. 26A-26E. For example: thewhistle sample inlet 2812 may correspond to the whistle sample inlet 212and/or the whistle sample inlet 2612; the whistle mouthpiece 2810 maycorrespond to the whistle mouthpiece 210 and/or the whistle mouthpiece2610; etc. While some components may be similar, or even identicalbetween the sample collection whistle 2800 and the sample collectionwhistle 200 and/or the sample collection whistle 2600, none are requiredto be similar, substantially similar, or identical.

FIGS. 28A-28C show a sample collection whistle 2800 without a samplecollection cartridge, e.g., without a sample capture cartridge 100. FIG.28A shows a front-top biased three-quarters view of the samplecollection whistle 2800. FIG. 28B shows a right side view of the samplecollection whistle 2800. FIG. 28C shows a top view of the samplecollection whistle 2800. As shown in FIG. 28A, the sample collectionwhistle 2800 has at its proximal end a whistle mouthpiece 2810 defininga whistle sample inlet 2812. As disclosed herein, when being used tocollect a breath sample, a user may blow into (e.g., place his/her lipsaround the whistle mouthpiece 2810 and exhale into) the whistle sampleinlet 2812 and into the whistle mouthpiece 2810 to take a breath sample.

At its distal end, the sample collection whistle 2800 has a cartridgesocket 2824 and a whistle back 2840 (shown clearly in FIG. 28B). Thecartridge socket 2824 is configured to accept a sample collectioncartridge, e.g., a sample capture cartridge 100, as disclosed herein. Toretain the sample capture cartridge within the sample collection whistle2800, the cartridge socket 2824 may have one or both of a frontcartridge retaining clip 2842 and a back cartridge retaining clip 2844.Either one or both of the back cartridge retaining clip 2844 and thefront cartridge retaining clip 2842 may have a lip configured to extendover and hold a portion of a sample collection cartridge. In someembodiments, the back cartridge retaining clip 2844 minimizes contactwith or does not contact the lens cap window 112 so as to advantageouslyprevent damage to the window that may cause noise or artifacts insubsequent reading of the sample.

In some embodiments, either one or both of the back cartridge retainingclip 2844 and the front cartridge retaining clip 2842 has an indexingfeature(s) configured to retain the sample collection cartridge in acertain (e.g., rotational) orientation during sampling. For example, theback cartridge retaining clip 2844 may have one or more small tabsconfigured to fit within the one or more lens cap vents 114 of thesample capture cartridge 100 and prevent rotation of the sample capturecartridge 100 during sampling.

Between the proximal end and the distal end, the sample collectionwhistle 2800 has a whistle body 2820. Additionally, on top of the samplecollection whistle 2800 is a whistle button 2850. In some embodiments,the whistle button 2850 is used, at least in part, to segment the user'sbreath. For example, the user's breath is vented until the user pressesthe button, at which time, the user's breath is passed through thesample collection cartridge.

In some embodiments, as shown in FIG. 28C, the sample collection whistle2800 includes an under-cartridge LED 2830. The under-cartridge LED 2830may be used to illuminate the sample capture cartridge 100. In someembodiments, the illumination of the sample capture cartridge 100provided by the under-cartridge LED 2830 may be provided for decorativepurposes. In some embodiments, the under-cartridge LED 2830 serves as apower indicator, e.g., when the sample collection whistle 2800 ispowered on or prepared to take a sample, the under-cartridge LED 2830 islit, but when the sample collection whistle 2800 is powered off or notprepared to take a sample, the under-cartridge LED 2830 is not lit. Insome embodiments, the sample collection whistle 2800 includes variouselectronics and power portions, e.g., battery or power cord, as may beneeded to operate the various components discussed herein.

In some embodiments, the sample collection whistle 2800 includes aspeaker or noise-maker that may be configured to provide auditorysignals to a user of the sample collection whistle 2800. For example,the speaker or noise-maker may be configured to beep to signal the userto take an action or stop an action. Any various other types ofsignaling may be used to communicate commands or instructions to theuser, for example visual, haptic, or auditory signals may be used (e.g.,lights, buzzers, beeps, etc.).

FIG. 29A shows the sample collection whistle 2800 shown in FIG. 28A witha sample capture cartridge 100 loaded into the 2824 and held down by thefront cartridge retaining clip 2842 (at the bottom of the sample capturecartridge 100). As can be seen, the front cartridge retaining clip 2842may provide a lip under which the edge, e.g., the bottom edge, of thesample capture cartridge 100 may fit and be held, e.g., securely held.

FIG. 29B illustrates the sample collection whistle 2800 shown in FIG.28B with a sample capture cartridge 100 loaded into the cartridge socket2824 and held by the back cartridge retaining clip 2844 (e.g., at thetop of the sample capture cartridge 100) and held down by the frontcartridge retaining clip 2842 (at the bottom of the sample capturecartridge 100). Again, it is clearly shown that the front cartridgeretaining clip 2842 may provide a lip under which the edge, e.g., thebottom edge, of the sample capture cartridge 100 may fit and be held,e.g., securely held. Furthermore, it may be seen that the back cartridgeretaining clip 2844 provides a lip or hook that extends over a least aportion of the top of the sample capture cartridge 100 to hold it duringsample collection.

FIG. 29C illustrates the sample collection whistle 2800 shown in FIG.28C with a sample capture cartridge 100 loaded into the cartridge socket2824 and held by the front cartridge retaining clip 2842 and the backcartridge retaining clip 2844. With reference to FIGS. 28C and 29C, itwill be appreciated that when a translucent sample capture cartridge 100(or a sample capture cartridge 100 having a translucent cartridge lenscap 110 or a translucent cartridge desiccant canister 140) is inserted,the under-cartridge LED 2830 may cause the sample capture cartridge 100to “glow” when the under-cartridge LED 2830 is turned on. Such “glowing”of the sample capture cartridge 100 may be used to signal the user totake an action or to stop an action. Alternatively, the “glowing” of theLED 2830 or the sample capture cartridge 100 may indicate that thewhistle is ready to receive a breath sample from the user.

FIGS. 30A-30C are cross-sectional views of the sample collection whistle2800. FIG. 30A illustrates the sample collection whistle 2800 of FIG.28C taken along line J-J, e.g., this figure shows a mid-linecross-section with no sample capture cartridge 100 in place within thecartridge socket 2824. FIG. 30B illustrates the sample collectionwhistle 2800 of FIG. 29C taken along line K-K, e.g., this figure shows amid-line cross-section with a sample capture cartridge 100 in placewithin the cartridge socket 2824 (except for the presence/absence of thesample capture cartridge 100, FIGS. 30A and 30B are the same.). FIG. 30Cillustrates the sample collection whistle 2800 of FIG. 29C taken alongline L-L.

As may be seen from the cross-sectional views of FIGS. 30A-30C, thesample collection whistle 2800 includes a sample conduit 2860 thatconnects the whistle mouthpiece 2810 and the whistle sample inlet 2812to the front cartridge retaining clip 2842. The sample conduit 2860 maybe a flexible hose. In some embodiments, the sample conduit 2860 is arubber hose. The proximal end of the sample conduit 2860 connects orcouples to the whistle mouthpiece 2810 and the whistle sample inlet2812. The distal end of the sample conduit 2860 terminates at the frontcartridge retaining clip 2842. Due to its, at least partially, flexiblenature, the distal end of the sample conduit 2860 may also serve as agasket or sealing ring against which the sample capture cartridge 100may be pushed and held by the back cartridge retaining clip 2844. Inthis way, the distal end of the sample conduit 2860 may serve as areplacement for the cartridge sealing grommet 214 and/or the cartridgesealing grommet 2614 of the sample collection whistle 200 and the samplecollection whistle 2600, respectively. As shown in FIG. 30B, to load thesample capture cartridge 100 into the sample collection whistle 2800,the bottom edge of the sample capture cartridge 100 may be slipped underthe front cartridge retaining clip 2842 and against the distal end ofthe sample collection whistle 2800 and pushed into the distal end of thesample collection whistle 2800 so that the proximal end of the samplecapture cartridge 100 may slip under the back cartridge retaining clip2844. The tight fit between the sample capture cartridge 100 and thedistal end of the sample collection whistle 2800 may serve to seal orsubstantially seal the bottom of the sample capture cartridge 100 to thedistal end of the sample collection whistle 2800 (e.g., with an airtightor substantially airtight seal).

The sample collection whistle 2800 includes a hole on its dorsal, ortop, side through which the button extension 2851 of the whistle button2850 extends. As shown most clearly in FIG. 30C, an exhaust vent 2885surrounds the button extension 2851 allowing gases to exhaust or ventaround the button extension 2851 and past the whistle button 2850.

The sample collection whistle 2800 includes two flow paths through whichgases may flow. The first flow path, or the exhaust or venting flow pathstarts at the whistle mouthpiece 2810, and enters through the whistlesample inlet 2812, passes through the exhaust vent 2885 in the top ofthe 2880, and goes past the whistle button 2850 (e.g., when the whistlebutton 2850 is not depressed to seal the whistle button 2850). Thesecond flow path, or the sample collection flow path, starts, again, atthe whistle mouthpiece 2810, and enters through the whistle sample inlet2812, passes through the length of the sample conduit 2860 and entersthe sample capture cartridge 100 where, because of the seal formedbetween the bottom of the sample capture cartridge 100 and the distalend of the sample conduit 2860, it passes through the sample capturecartridge 100 and exits through the lens cap vents 114.

In some embodiments, the exhaust or venting flow path has an openconfiguration and a closed configuration. The whistle button 2850 servesas an on/off switch, or flow reducer, for the exhaust vent 2885 (e.g.,on, off, or modulation between the two). When the whistle button 2850 isnot being pushed or depressed, the exhaust vent 2885 is fully open. Whenthe whistle button 2850 is being pushed or depressed (e.g., pushed ordepressed fully), the whistle button 2850 is configured to push downagainst the outer surface of the top of the sample conduit 2860 andseal, or substantially seal, the exhaust vent 2885 (e.g., with anairtight or substantially airtight seal).

When the whistle button 2850 is not depressed and the exhaust vent 2885is fully open and a sample capture cartridge 100 is present, the samplecapture cartridge 100 provides a substantial amount of flow resistance,such that the resistance to flow of the exhaust or venting flow path isless, e.g., significantly less, than the resistance to flow of thesample collection flow path. When the whistle button 2850 is notdepressed and the exhaust vent 2885 is fully open, the amount of flowpassing through the exhaust or venting flow path and to the atmosphereis at least about 80%, at least about 85%, at least about 87.5%, atleast about 90%, at least about 92.5%, at least about 95%, at leastabout 97.5%, or at least about 99%.

When the whistle button 2850 is depressed, the whistle button 2850 maymate, e.g., closely mate or sealingly mate (e.g., with an airtight orsubstantially airtight seal), with the exhaust vent 2885 such that theflow through the exhaust or venting flow path is decrease by at leastabout 80%, at least about 85%, at least about 87.5%, at least about 90%,at least about 92.5%, at least about 95%, at least about 97.5%, or atleast about 99%.

As discussed herein, the sample conduit 2860 may be flexible. Suchflexibility allows the button extension 2851 of the whistle button 2850to push down on an interior, ventral, surface of the sample conduit 2860sufficiently such that push button 2832 below the sample conduit 2860 isactivated. In this way, push button 2832 serves as feedback to identifywhen the whistle button 2850 is being pushed. Alternatively stated, thepush button 2832 may serve as feedback to identify when gases, e.g.,breath, is passing through the exhaust or venting flow path, or whengases, e.g., breath, is passing through the sample collection flow path.

The sample collection whistle 2800 may be used to segment breath samplesso that deep-lung samples may be selectively collected. In operation, auser may insert a sample capture cartridge 100, e.g., a disposablereplaceable cartridge, into the cartridge socket 2824 of the samplecollection whistle 2800 by pushing it against the distal end of thesample conduit 2860 and under the lip of the front cartridge retainingclip 2842. The user may push the sample capture cartridge 100 againstthe sample conduit 2860 sufficiently hard that the top of the samplecapture cartridge 100 may slip or fit under the back cartridge retainingclip 2844.

The sample collection whistle 2800 may be turned on in any of a numberof ways, similar to those of other sample collection whistles disclosedherein. In operation, a sample capture cartridge 100 may inserted intothe sample collection whistle 2800 and the sample collection whistle2800 may be turned on. The sample collection whistle 2800 signals theuser when to begin blowing into the whistle mouthpiece 2810, forexample, by using an aural tone (e.g., a beep) or a light (e.g., aflashing light or a light of a certain color). As the user blows intothe sample collection whistle 2800, the breath is exhausted (orprimarily exhausted) out of the exhaust vent 2885 because of its lowerresistance to flow. The sample collection whistle 2800 will registerthat the breath is being exhausted because the push button 2832recognizes the presence or absence of the button extension 2851 of thewhistle button 2850, which is correlated to opening and closing,respectively of the exhaust vent 2885.

As disclosed herein, various types of signals may be presented to theuser as instructions or cues. For example, the various sample collectionwhistles disclosed herein may use an aural tone (e.g., a beep) or alight (e.g., a flashing light or a light of a certain color). Any of thevarious sample collection whistles disclosed herein may also include oneor more of a processor and a speaker or a processor and a transmitterconfigured to transmit a signal ultimately to a speaker. For example,the sample collection whistle may include a processor and a speaker. Thesample collection whistle may include only a processor and atransmitter, the processor and speaker configured to transmit a signalto one or more of a processor and a speaker external to the samplecollection whistle (e.g., in a mobile device such as a smart phone). Theprocessor and speaker (and transmitter, if present) may be configured toprovide instructions to a user in any language (e.g., any languageprogrammed into the processor). For example, the processor and speakermay be configured to provide audio instructions to the user, including,but not limited to: “press the button,” “hold and exhale,” “testcomplete,” etc. The instructions provided to the user may be responsiveto one or more conditions sensed and or reported by the samplecollection whistle, including, but not limited to time, volume of fluidpassing through the whistle, flow rate of fluid passing through thewhistle, etc.

When the sample collection whistle 2800 detects, as is disclosed herein,that the desired breath segment has been reached, the sample collectionwhistle 2800 may change the signal to the user signaling the user todepress the whistle button 2850. When the whistle button 2850 isdepressed, the exhaust vent 2885 is closed and the breath sample isforced through the sample capture cartridge 100. The sample collectionwhistle 2800 will register the flow path change because the push button2832 will be activated by the button extension 2851 of the whistlebutton 2850 when the user presses the whistle button 2850. In someembodiments, the push button 2832 will not be properly activated untilthe whistle button 2850 is pressed down sufficiently far to effectivelyor substantially seal the exhaust vent 2885 (e.g., an airtight seal).

In some embodiments, when the sample collection whistle 2800 detects aflow path change (e.g., from exhausting to sample collection), it beginscounting down the proper sample collection duration. The whistle mayinclude a programmed controller that handles or controls the task ofcounting down the proper sample duration and any of the other varioussignaling tasks that may be required. Sample collection duration may bebased on such factors as time, flow rate, flow volume, etc., asdisclosed herein. In some embodiments, when the sample collectionwhistle 2800 detects a flow path change (e.g., from exhausting to samplecollection), it changes a signal to the user, e.g., the visual, haptic,or auditory signal is changed. For example, when the sample collectionwhistle 2800 detects that sufficient breath has vented, the samplecollection whistle 2800 may change from a beeping noise at a given toneto a sustained noise at a different tone. In some embodiments, when thesample collection whistle 2800 has detected that a sufficient sample hasbeen collected, as disclosed herein, it again changes a signal to theuser, e.g., the visual, haptic, or auditory signal is changed. In thisway, the sample collection whistle 2800 may be configured to signal tothe user when to begin or when to stop certain actions, including, butnot limited to exhalation, whistle button 2850 depression, whistlebutton 2850 release, etc.

In some embodiments, the various sample collection whistles disclosedherein may incorporate sensor circuitry and/or components for analyzinga sample collection cartridge. Additionally, the various samplecollection whistles disclosed herein may include a wireless transceiverfor communicating with any other device, e.g., a mobile device or phone.In some embodiments, the various sample collection whistles disclosedherein may incorporate sufficient circuitry, components, transceivers,and/or sensors that no base unit or separate sample collection cartridgeanalyzer is needed to analyze the used sample collection cartridge(s),e.g., the sample collection whistle may be configured to both facilitatecollection of the sample in the sample collection cartridge (e.g.,segmenting and directing the breath) and analyze the sample collected bythe sample collection cartridge.

Some embodiments of the sample collection whistles disclosed herein areportable, small, or hand-held devices. In some embodiments, the samplecollection whistle is less than about 10 cm long. In some embodiments,the sample collection whistle is shorter than about 20 cm, shorter thanabout 19.5 cm, shorter than about 19 cm, shorter than about 18.5 cm,shorter than about 18 cm, shorter than about 17.5 cm, shorter than about17 cm, shorter than about 16.5 cm, shorter than about 16 cm, shorterthan about 15.5 cm, shorter than about 15 cm, shorter than about 14.5cm, shorter than about 14 cm, shorter than about 13.5 cm, shorter thanabout 13 cm, shorter than about 12.5 cm, shorter than about 12 cm,shorter than about 11.5 cm, shorter than about 11 cm, shorter than about10.5 cm, shorter than about 10 cm, shorter than about 9.5 cm, shorterthan about 9 cm, shorter than about 8.5 cm, shorter than about 8 cm,shorter than about 7.5 cm, shorter than about 7 cm, shorter than about6.5 cm, shorter than about 6 cm, shorter than about 5.5 cm, shorter thanabout 5 cm, shorter than about 4.5 cm, shorter than about 4 cm, shorterthan about 3.5 cm, shorter than about 3 cm, shorter than about 2.5 cm,or shorter than about 2 cm. In some embodiments, the sample collectionwhistle weighs less than about 300 grams, less than about 280 grams,less than about 260 grams, less than about 240 grams, less than about220 grams, less than about 200 grams, less than about 180 grams, lessthan about 160 grams, less than about 140 grams, less than about 120grams, less than about 100 grams, less than about 80 grams, less thanabout 60 grams, or less than about 40 grams.

1 Piece Breather

The various sample capture cartridges 100 disclosed herein may be usedwith any of a number of cartridge holders and/or sample collectors. Forexample, some embodiments of the sample capture cartridge 100 areconfigured to be used with a sample collection whistle 200 as disclosedherein. The sample collection whistle 200 may be advantageouslyre-usable for a number of reasons. For example, the sample collectionwhistle 200 may be relatively complex, it may incur more than acomparatively low, e.g., de minimis cost, it may be particularly wellsuited towards segmenting samples, etc. In some embodiments, it may beadvantageous to use a sample collection/capture cartridge with a simplerand/or disposable cartridge holder. For example, in some instancessample segmentation may not be particularly important. Rather, the merepresence and/or identification of an analyte of interest, irrespectiveof time, may be the primary objective. Additionally, it may beadvantageous to have a cartridge holder that may be disposable, e.g., issmall and relatively inexpensive. For example, point of care testers mayneed to use a new cartridge holder with each patient they see, i.e., fora number of reasons they may not be able to sterilize and re-use acartridge holder. In such cases, a cartridge holder such as the samplecollection whistle 200 may prove too complex and/or expensive fordisposal. In such cases a one piece breather may advantageously be used.

FIGS. 12A and 12B illustrate front and rear views of an unassembled onepiece breather 300. With reference to FIG. 12B, the one piece breather300 includes, at its core a breather body 310 having a grommet ridge 314and a breather body cartridge port 316. The grommet ridge 314 isconfigured to accept and hold a cartridge sealing grommet 302, such asthat shown in FIG. 12C.

The cartridge sealing grommet 302 may be used to help seal a samplecollection cartridge to the one piece breather 300 to prevent leakage ofsample between the sample collection cartridge (e.g., a sample capturecartridge 100) and the one piece breather 300. As will be readilyunderstood, other structures or features may be used to accomplishsimilar ends. As such, some embodiments of the one piece breather 300 donot include a cartridge sealing grommet 302 (or the grommet ridge 314that may be used to hold the cartridge sealing grommet 302). Thecartridge sealing grommet 302, an example of which is shown in FIG. 12C,may have a grommet groove 304 and a grommet port 306. The cartridgesealing grommet 302 may snap into the breather body 310 such that thegrommet groove 304 lies over and grips the grommet ridge 314. Thecartridge sealing grommet 302 may function similarly to the cartridgesealing grommet 214 discussed in connection with the sample collectionwhistle 200. As with that cartridge sealing grommet 214, the cartridgesealing grommet 214 may be a lower durometer material, such as a rubber,that is configured to advantageously form a tight seal with a samplecollection cartridge (e.g., the cartridge desiccant canister 140 of thesample capture cartridge 100) (e.g., the cartridge sealing grommet 214has a diameter that is larger than the diameter of the cartridgedesiccant canister 140 of the sample capture cartridge 100 such that theentire perimeter of the lower surface or ring of the cartridge desiccantcanister 140 may be effectively pressed into the cartridge sealinggrommet 214).

With continued reference to FIG. 12B, the one piece breather 300 mayhave two side wings, a first breather wing 320 and a second breatherwing 340. One of ordinary skill in the art will understand that variousand/or numerous modifications may be made to the one piece breather 300and various and/or numerous different or alternative structures may beused to accomplish many, if not all, of the functions of the one piecebreather 300 disclosed in FIG. 12B. The one piece breather 300 may beproduced (e.g., molded, extruded, etc.) and/or provided (e.g., to theuser or point of care provider) in the configuration shown in FIG. 12B,e.g., with the wings first breather wing 320 and second breather wing340 extending from the breather body 310 in a substantially orapproximately perpendicular fashion.

Starting from the end of the first breather wing 320 closest to thebreather body 310 of the one piece breather 300, in some embodiments thefirst breather wing 320 includes a first wing first hinge 322, a firstwing first spring 326, a first wing snap hole 338, a first wing ramp332, a first wing second hinge 324, a first wing paddle 334, a firstwing snap 330, a first wing second spring 328, and a first wingcartridge ejector 336. Starting from the end of the second breather wing340 closest to the breather body 310 of the one piece breather 300, insome embodiments the second breather wing 340 includes a second wingfirst hinge 342, a second wing first spring 346, a second wing snap hole358, a second wing ramp 352, a second wing second hinge 344, a secondwing paddle 354, a second wing snap 350, a second wing second spring348, and a second wing cartridge ejector 356. In some embodiments, thefirst breather wing 320 and the second breather wing 340 are bilaterallysymmetrical. In some embodiments, the first breather wing 320 and thesecond breather wing 340 may be different. For example, in someembodiments, one of the wings may be fixed and molded while only theother wing is movable.

Turning to FIG. 12A, the one piece breather 300 is shown from the rear,e.g., the end into which the sample may be directed during use. As canbe seen, the breather body 310 includes a breather body inlet 312 intowhich the sample may be directed during use, e.g., into which a patientmay blow. In some embodiments, the breather body 310 may have across-sectional diameter that renders the one piece breather 300 handheld. For example the breather body 310 may have a cross-sectionaldiameter of between about 5-30 mm, between about 5.5-28 mm, betweenabout 6-26 mm, between about 6.5-24 mm, between about 7-22 mm, betweenabout 7.5-20 mm, between about 8-18 mm, between about 8.5-16 mm, betweenabout 9-14 mm, between about 9.5-12 mm, or any other diameter thatadvantageously facilitates use and collection of samples as disclosedherein. The one piece breather 300 in FIG. 12A is shown with the secondbreather wing 340 in its extended (e.g., perpendicular) conformationwhile the first breather wing 320 is shown partially folded.

In operation, to prepare the one piece breather 300 for use, the firstbreather wing 320 and the second breather wing 340 may be folded in onthemselves. In some embodiments, the first wing first hinge 322 and thefirst wing second hinge 324 are bent so that the first wing snap 330swings toward the first wing snap hole 338. The first wing snap 330 maysnap fully into the first wing snap hole 338, thereby holding theportion of the first breather wing 320 distal to the first wing secondhinge 324 (distal being defined as away from the breather body 310 ofthe one piece breather 300) proximal/close/in contact to/with theportion of the first breather wing 320 proximal to the first wing secondhinge 324. In much the same way, the second wing first hinge 342 and thesecond wing second hinge 344 are bent so that the second wing snap 350swings toward the second wing snap hole 358. The second wing snap 350may snap fully into the second wing snap hole 358, thereby holding theportion of the second breather wing 340 distal to the second wing secondhinge 344 (distal again being defined as away from the breather body 310of the one piece breather 300) proximal proximal/close/in contactto/with the portion of the second breather wing 340 proximal to thesecond wing second hinge 344. The various hinges or pivot points of theone piece breather 300, e.g., the first wing first hinge 322, first wingsecond hinge 324, second wing first hinge 342, and second wing secondhinge 344, may be living hinges, or any other type of hinge thatprovides sufficient connection and retention as will be readilyunderstood by one of ordinary skill in the art.

The portion of the first breather wing 320 (or corresponding portions ofthe second breather wing 340) distal to the first wing second hinge 324may be held to the portion of the first breather wing 320 proximal tothe first wing second hinge 324 using any type of connection means knownto one of ordinary skill in the art. The figures illustrate a prongedsnap/clip being used (e.g., first wing snap 330) that is shoved intofirst wing snap hole 338. However, any type of fixation or connectionmay be used, including, without limitation, ramp/step clips on theedge(s) of the first breather wing 320, adhesives, prongs, hooks,buttons, snaps, etc.

FIGS. 13A and 13B illustrate an embodiment of the one piece breather 300ready for use, e.g., folded into a configuration in which the one piecebreather 300 may accept a sample collection cartridge, such as thesample capture cartridge 100 of FIG. 1 (e.g., the first breather wing320 has been fixed to itself using the first wing snap 330 and firstwing snap hole 338 and the second breather wing 340 has been fixed toitself using the second wing snap 350 and the second wing snap hole358). FIG. 13A shows the one piece breather 300 ready to accept a samplecollection cartridge while FIG. 13B shows the one piece breather 300into which the sample capture cartridge 100 has been placed.

As will be understood with Reference to FIGS. 13A and 12A, the firstbreather wing 320 and the second breather wing 340 may be held in aninwardly-biased configuration, e.g., with the first wing ramp 332 andthe second wing ramp 352 held close towards each other. Such aninwardly-biased configuration may be facilitated, at least in part, bythe first wing second spring 328 of the first breather wing 320 and thesecond wing second spring 348 of the second breather wing 340. Thesesprings help force the first wing first hinge 322 and second wing firsthinge 342, respectively, inward to hold the ramps, e.g., the first wingramp 332 and the second wing ramp 352 close toward each other. When asample collection cartridge is to be loaded into the one piece breather300, the ramps may be forced apart from each other, thereby compressingthe first wing second spring 328 of the first breather wing 320 and thesecond wing second spring 348 of the second breather wing 340.

The first wing ramp 332 and the second wing ramp 352 act as a combinedramped interface with an upper edge of a sample collection cartridge. Assuch, when the first breather wing 320 and the second breather wing 340are brought closer to each other, e.g., by applying pressure to thefirst wing paddle 334 and the second wing paddle 354, the first wingramp 332 and the second wing ramp 352 push “down” on the samplecollection cartridge. Each ramp, e.g., first wing ramp 332 and secondwing ramp 352, have a ramp angle defined as the angle between theapproximately 90 degree outer-most surface of the ramp and the ramped,inward surface (e.g., that interfaces with or contacts the samplecollection cartridge). As will be readily understood, the smaller theramp angle, the more force is placed on the sample collection cartridgewhen the ramps are brought closer to each other. By extension, thelarger the ramp angle, the less force is placed on the sample collectioncartridge when the ramps are brought closer to each other. The ramps,e.g., the first wing ramp 332 of the first breather wing 320 and thesecond wing ramp 352 of the second breather wing 340 may have any anglethat advantageously facilitates loading and compression of a samplecollection cartridge, e.g., a sample capture cartridge 100, within theone piece breather 300. But, in any event, the ramp angle is less than90 degrees (e.g., a flat surface parallel to the inner surface of therespective wing, e.g., the first breather wing 320 or the secondbreather wing 340). In some embodiments, the ramp angle is about 45degrees. In some embodiments, the ramp angle is less than about 85degrees, less than about 80 degrees, less than about 75 degrees, lessthan about 70 degrees, less than about 65 degrees, less than about 60degrees, less than about 55 degrees, less than about 50 degrees, lessthan about 45 degrees, less than about 40 degrees, less than about 35degrees, less than about 30 degrees, less than about 25 degrees, lessthan about 20 degrees, less than about 15 degrees, or less than about 10degrees. In some embodiment, the ramp angle is in the range of betweenabout 20-60 degrees, between about 22-58 degrees, between about 24-56degrees, between about 26-54 degrees, between about 28-52 degrees,between about 30-50 degrees, between about 32-48 degrees, between about34-46 degrees, between about 36-44 degrees, or between about 38-42degrees.

FIG. 14A illustrates a sample capture cartridge 100 being loaded into anembodiment of a one piece breather 300. In some embodiments, the firstwing cartridge ejector 336 and the second wing cartridge ejector 356 maybe simultaneously squeezes to bring the first wing cartridge ejector 336and the second wing cartridge ejector 356 closer to the breather body310 and provide space between the first wing ramp 332 and the secondwing ramp 352 through which the sample capture cartridge 100 may pass.Once the sample capture cartridge 100 has passed the first wing ramp 332and the second wing ramp 352, the pressure on the first wing cartridgeejector 336 and second wing cartridge ejector 356 may be release atwhich time the first wing second spring 328 and the second wing snaphole 358 may bias the first breather wing 320 and the second breatherwing 340 such that the first wing ramp 332 and the second wing ramp 352gently hold the sample capture cartridge 100 in place in the breatherbody cartridge port 316 (shown in both FIGS. 14A and 13B).

In some embodiments, the first breather wing 320 and the second breatherwing 340 are configured to allow enough movement between the samplecapture cartridge 100 and the breather body cartridge port 316 and/orthe cartridge sealing grommet 302 (when present) that airflow ispermitted around the sample capture cartridge 100. Thus, when a samplecapture cartridge 100 is present and the first breather wing 320 and thesecond breather wing 340 are in their relaxed configurations (e.g., noexternal forces being applied), a sample fluid may enter the breatherbody inlet 312, pass through the breather body cartridge port 316 andflow around the sample capture cartridge 100, rather than being forcedthrough the sample capture cartridge 100 (e.g., by exploiting the pathof least resistance).

Turning to FIG. 14B, when an inward force is applied to the firstbreather wing 320 and the second breather wing 340, e.g., a force isapplied to one or more of the first wing paddle 334 and the second wingpaddle 354, the first wing ramp 332 and the second wing ramp 352 arebrought closer to each other. As discussed herein, when the first wingramp 332 and second wing ramp 352 are brought closer to each other, theramps exert a downward/inward force on the sample capture cartridge 100,thereby pushing it towards or onto the breather body cartridge port 316and/or cartridge sealing grommet 302 (when present). When the samplecapture cartridge 100 is pressed onto/into the breather body cartridgeport 316 and/or the cartridge sealing grommet 302, the base of thesample capture cartridge 100 may seal against the breather bodycartridge port 316 and/or the cartridge sealing grommet 302, therebyforcing any sample fluid that is forced into the breather body inlet 312to pass through the breather body inlet 312, through the breather bodycartridge port 316, and through and out of the sample capture cartridge100.

Turning to FIG. 14C, the first wing cartridge ejector 336 and secondwing cartridge ejector 356 may be squeezes (e.g., brought closer to thebreather body 310) to allow ejection of the sample capture cartridge100. For example, after a sample is collected or if, for whateverreason, a user desires to ejection the sample capture cartridge 100, thefirst wing cartridge ejector 336 and second wing cartridge ejector 356may be squeezed to cause the first wing ramp 332 and second wing ramp352 to separate and allow passage of the sample capture cartridge 100between the ramps.

In operation and to use the one piece breather 300, a user may squeezethe first wing cartridge ejector 336 and second wing cartridge ejector356, compressing the first wing second spring 328 and the second wingsecond spring 348 and causing the distance between the first wing ramp332 and the second wing ramp 352 to increase (e.g., causes the wings toopen or flare). The user may then insert a sample collection cartridge,e.g., a sample capture cartridge 100, between the first wing ramp 332 ofthe first breather wing 320 and the second wing ramp 352 of the secondbreather wing 340. Once the sample collection cartridge has completelypassed the ramps, the user may release (e.g., cease inward pressure orforce on) the first wing cartridge ejector 336 and the second wingcartridge ejector 356. The first wing second spring 328 and the secondwing second spring 348 will then bias the first breather wing 320 andthe second breather wing 340 gently inward (e.g., so that the first wingramp 332 and the second wing ramp 352 are gently biased toward eachother) so that the sample capture cartridge 100 is held loosely in thebreather body cartridge port 316 between the two wings, first breatherwing 320 and second breather wing 340. The user may cause a flow ofsample fluid to enter into the breather body inlet 312 of the one piecebreather 300. However, as discussed above, before pressure is applied tothe second wing paddle 354 of the second breather wing 340 and the firstwing paddle 334 of the first breather wing 320 the sample fluid willflow between the breather body cartridge port 316 and the loosely-heldsample capture cartridge 100. When the user is ready to collect aportion of the sample using the sample capture cartridge 100, the usermay apply a force to the first wing paddle 334 of the first breatherwing 320 and the second wing paddle 354 of the second breather wing 340(e.g., the user may squeeze the two paddles with her fingers). Asdiscussed herein, when the user squeezes the paddles, the first wingramp 332 and the second wing ramp 352 will force the sample capturecartridge 100 toward and against the breather body cartridge port 316and/or the cartridge sealing grommet 302, thereby sealing the samplecapture cartridge 100 against the breather body cartridge port 316and/or the cartridge sealing grommet 302 and forcing the sample to passthrough the sample capture cartridge 100. In this way, a user may beable to segment a sample (e.g., the user may blow into the breather bodyinlet 312 then, partially through the breath, the user may squeeze thepaddles to begin collection of a desired breath segment, e.g., a deepalveolar sample). Once the collection is complete, the user may squeeze(e.g., apply a force to or on) the first wing cartridge ejector 336 andthe second wing cartridge ejector 356, thereby biasing the first wingramp 332 and the second wing ramp 352 apart, e.g., away from each other,so that the sample capture cartridge 100 might pass through the rampsand be removed from the one piece breather 300, e.g., as shown in FIG.14C. Finally, the one piece breather 300 may be discarded (though thisis not necessary).

Rapid Test Sample Collection Cartridge and Sponge-Based Delivery ofDeveloper Solution

A number of separable sample collection cartridges and sample collectionwhistles (sample collection cartridge holders) are disclosed herein. Asdiscussed, to use some of these separable systems, the sample collectioncartridge may be inserted into the sample collection whistle, a samplefluid may be forced through the sample collection whistle (e.g., holder)and the sample collection cartridge, the sample collection cartridgeremoved from the sample collection whistle, and the collected sampleevaluated. In some embodiments, it may be advantageous to use a rapidtest sample collection cartridge that eliminates one or more stepsneeded to use the separable system. For example, in some instancessample segmentation may not be particularly important. Rather, the merepresence and/or identification of an analyte of interest, irrespectiveof time, may be the primary objective. Moreover, the speed of detectionmay be a primary objective. Additionally, it may be advantageous toentirely eliminate the collection whistle. For example, point of caretesters may need a binary test (present/not present, orpositive/negative) that they may use quickly and/or with young,inexperienced, or difficult patients. In such cases, a cartridge holdersuch as the sample collection whistle 200 may prove too complex and/ortime consuming. In such cases a rapid test sample collection cartridgemay advantageously be used.

A rapid test sample collection cartridge 400 may include a collectioncartridge body 410. As shown in FIG. 15A, the collection cartridge body410 may be similar to the breather body 310 of the one piece breather300, except without the wings first breather wing 320 and secondbreather wing 340. The collection cartridge body 410 may also be ahollow body with a collection cartridge body port 416 through which afluid sample may be passed. Unlike the breather body 310 of the onepiece breather 300, the collection cartridge body 410 of the rapid testsample collection cartridge 400 is not configured to accept and/or holda sample collection cartridge. The collection cartridge body 410 of therapid test sample collection cartridge 400 may include a samplecollection portion build directly into the collection cartridge body410. The rapid test sample collection cartridge 400 is similar to anintegral combination of a one piece breather 300 and a sample capturecartridge 100.

In some embodiments, the collection cartridge body 410 may have across-sectional diameter that renders the rapid test sample collectioncartridge 400 hand held. For example the collection cartridge body 410may have a cross-sectional diameter of between about 5-30 mm, betweenabout 5.5-28 mm, between about 6-26 mm, between about 6.5-24 mm, betweenabout 7-22 mm, between about 7.5-20 mm, between about 8-18 mm, betweenabout 8.5-16 mm, between about 9-14 mm, between about 9.5-12 mm, or anyother diameter that advantageously facilitates use and collection ofsamples as disclosed herein. The rapid test sample collection cartridge400 may have a length that renders the rapid test sample collectioncartridge 400 easy to hold, manipulate, use, etc. For example the rapidtest sample collection cartridge 400 has a length of about 30 mm. Insome embodiments, the rapid test sample collection cartridge 400 has alength of between about 10-100 mm, between about 15-90 mm, between about20-80 mm, between about 25-70 mm, between about 30-60 mm, between about35-50 mm, or any other length that advantageously facilitates use andcollection of samples as disclosed herein.

The collection cartridge body 410 may include a sample collection fritor structure 430 that is configured to pass the sample fluid whilecollecting an analyte of interest. In some embodiments, the samplecollection frit 430 is similar to the blended bowl discussed herein. Asshown in FIG. 15B, and as discussed in connection with the blended bowl,the sample collection frit 430 may comprise a porous base material 432holding functionalized silica beads 420. When the analyte of interestpasses through the porous base material 432 of the sample collectionfrit 430, it interacts with, e.g., passes by or contacts, thefunctionalized silica beads 420 and some of the analyte of interestbinds with the silica 420. The binding of the analyte of interest withthe functionalized silica beads 420 is a reaction that may be detected,e.g., at the time of reaction or later (such as using a developersolution). In some embodiments, the reaction of the analyte of interestwith the functionalized silica beads 420 is analyzed using an opticalanalyzer, e.g., the reaction produces a change in the sample collectionfrit 430 that may be detected optically (such as color). For example,the frit 430 may be sequentially illuminated by each of multiple LEDs ofdifferent respective wavelengths or colors while a photodiode measuresthe light reflected from the frit at each such wavelength or color.

The rapid test sample collection cartridge 400 may also include acartridge desiccant retainer 460 and or desiccant 450. In someembodiments the cartridge desiccant retainer 460 is similar in structureand function to the cartridge desiccant retainer 160 of the samplecapture cartridge 100 (e.g., the cartridge desiccant retainer 460 mayhave: ports similar to the desiccant retainer ports 164 of the cartridgedesiccant retainer 160; a notch similar to the desiccant retainer notch162 of the cartridge desiccant retainer 160; and/or a bevel similar tothe desiccant retainer bevel 166 of the cartridge desiccant retainer160). In much the same way, the desiccant 450 may be similar in one ormore metrics (e.g., size, quantity, positioning, function, etc.) to thedesiccant 150 of the sample capture cartridge 100. In some embodiments,not shown, the rapid test sample collection cartridge 400 does notinclude either a cartridge desiccant retainer 460 or a desiccant 450. Insome embodiments, the rapid test sample collection cartridge 400 has twocartridge desiccant retainers 460 between which the desiccant 450 issandwiched, e.g., the collection cartridge body 410 holds a firstcartridge desiccant retainer 460, then a quantity of desiccant 450, thena second cartridge desiccant retainer 460, then the sample collectionfrit 430 containing the functionalized silica beads 420. In someembodiments, the rapid test sample collection cartridge 400 has only onecartridge desiccant retainer 460, but no desiccant 450. In suchembodiments, the cartridge desiccant retainer 460 may advantageously beprovided as support for a comparatively think sample collection frit430.

FIG. 16A-16B illustrate an embodiment of a rapid test sample collectioncartridge 400. The rapid test sample collection cartridge 400 of FIGS.16A-16B includes a collection cartridge body 410 having a collectioncartridge body inlet 414 at a proximal or first end of the collectioncartridge body 410. At the distal or second end (e.g., opposite thefirst end) of the collection cartridge body 410, the collectioncartridge body 410 holds a cartridge desiccant retainer 460, as can beseen in FIG. 16A. With reference to FIG. 16B, the collection cartridgebody 410 holds a sample collection frit 430 on its distal end. Betweenthe sample collection frit 430 and the cartridge desiccant retainer 460,not shown in either FIG. 16A or 16B, the collection cartridge body 410holds a quantity of desiccant 450 to absorb excess moisture from a fluidsample passed through the rapid test sample collection cartridge 400.

The rapid test sample collection cartridge 400 may be used to quicklyand easily collect a fluid sample, e.g., a breath sample. In operation,a subject may be instructed to blow through the rapid test samplecollection cartridge 400. The subject's breath will therefore be forcedinto the collection cartridge body inlet 414, and through the interiorof the collection cartridge body 410, through any cartridge desiccantretainer(s) 460 and desiccant 450 present, and through the samplecollection frit 430. The lid 702 and the base 704 may be closed toprevent the developer contained within the developer pad 710 from dryingout when the developer pad 710 is not in use.

The rapid test sample collection cartridge 400 may be used with a rapiddeveloper stamp pad 700, e.g., when a developing solution is needed oruseful to detect (e.g., to induce a detectable change, such as anoptically detectable change) the binding of the analyte of interest tothe functionalized silica beads 420. The rapid developer stamp pad 700may include at least a lid 702 and a base 704 which contain a developerpad 710. The developer pad 710 may be similar in structure and functionto an ink pad, e.g., it may comprise a sponge or solution holding pad orreservoir that contains a volume of a developer (an appropriatedeveloper that is configured to induce a detectable change, such as anoptically detectable change, in the sample collection frit 430when/after an analyte of interest has bound to the functionalized silicabeads 420). The sponge may, for example, be formed from a fibrousmaterial that can serve as a high release media; for instance, thesponge may be formed as a bonded fiber reservoir containing fibers ofpolyethylene and polypropylene. The average pore size of the sponge 710may be selected to be larger than the average pore size of the porousfrit or structure 430 to facilitate transfer of the developer solutionthrough capillary or wicking action. Preferably, the sponge material isselected or configured such that the porous structure is fully wettedwith developer solution less than 8 seconds, and more preferably lessthan 6 seconds (e.g., within 3 to 5 seconds), after the sponge andporous structure 430 are brought into contact with each other.

As shown in FIGS. 17A and 17B, after a sample has been collected, therapid developer stamp pad 700 may be used in conjunction with the usedrapid test sample collection cartridge 400 to analyze the sample. Asshown in FIG. 17A, the rapid test sample collection cartridge 400 islowered down onto the developer pad 710 of the rapid developer stamp pad700, e.g., manually lowered. As will be readily understood, so that thesample collection frit 430, which presumably bound some concentration oramount of the analyte of interest (e.g., onto the functionalized silicabeads 420) should be facing the developer pad 710 and the collectioncartridge body inlet 414 pointing away from the 710. As shown in FIG.17B, sample collection frit 430 of the used rapid test sample collectioncartridge 400 may be pushed into the developer pad 710 of the rapiddeveloper stamp pad 700. When the sample collection frit 430 of therapid test sample collection cartridge 400 is pushed into the developerpad 710, the developer contained within the developer pad 710 entersinto the porous body of the sample collection frit 430 andreacts/interacts with the sample collection frit 430 and the analyte ofinterest contained therein (e.g., the analyte of interest bound to thefunctionalized silica beads 420). Upon removal of the sample collectionfrit 430 of the rapid test sample collection cartridge 400 from thedeveloper pad 710 of the rapid developer stamp pad 700, the developermay induce a detectable change, such as an optically, thermally, etc.detectable change, in the sample collection frit 430. The change in thesample collection frit 430, e.g., the optically detectable change, maybe analyzed to determine the presence or absence of the analyte ofinterest within the sample collection frit 430 of the rapid test samplecollection cartridge 400.

This method of dispensing developer solution to a porous samplecollection frit or structure 430 following breath sample capture mayalso be used in other embodiments, including the other embodimentsdisclosed herein. For example, in some embodiments, the porous structure430 and pre-soaked sponge or pad 710 may be incorporated into adisposable cartridge with an air gap between the two, in which case theporous structure and sponge may be brought into contact with each other(e.g., by a manually applied force, or a force generated by a motor orsolenoid) after the breath sample is passed through the porous structure430. The porous structure 430 and sponge 710 in such cartridge-basedembodiments may each be in the shape of a puck or cylinder (as shown inFIGS. 15B, 36A and 36B) of like or similar diameter, in which case flatsurfaces of the two puck-shaped devices may be brought into contact witheach other to cause the transfer of the developer solution from thesponge to the porous structure.

One such arrangement is illustrated in FIGS. 36A and 36B. In FIG. 36A,which illustrates the arrangement before the developer solution isdispensed, a cylindrical sponge element 710 is held within a plastic cap365 with an air gap separating the sponge element 710 from thepuck-shaped porous structure or frit 430 containing the reactant. Thebottom surface of the porous structure 430 is in contact with atransparent window or lens 112 through which color changes can beobserved. Although not shown in the drawings, the sponge element 710,cap 365 and porous structure 430 may be housed within a disposabledevice that includes an air flow path for routing a breath samplethrough the porous structure 430 as the user exhales. For example, theillustrated arrangement may be housed within a single-use cartridge, orwithin a canister of a multi-canister/multi-day disposable. In theillustrated embodiment, the sponge element 710 has a greater volume thanthe porous structure 430.

As illustrated in FIG. 36B, after the breath sample is routed throughthe porous structure 430, a force-applying member or shaft 367, whichmay be activated manually or by a motor or solenoid, applies a force tothe cap 365, causing the sponge element 710 to come into contact withthe porous structure 430, and causing developer solution 369 held by thesponge element to flow into the porous structure 430. (The cap may slidewithin a tubular member that is omitted from the drawings.) The flowpreferably occurs by capillary action or wicking, and does not rely ongravity to properly wet the porous structure 430; thus, the porousstructure 430 is properly wetted regardless of the orientation of theillustrated assembly. In some embodiments, a color change or otheroptical change induced by the developer solution is measured through thewindow 112 by an optical subsystem (not shown). For example, one or moreLEDs may illuminate the porous structure 430 through the window 112while a photodiode measures the light reflected from the porousstructure, as described above. One example of a photodiode/LED assemblyand process that may be used in the various embodiments disclosed hereinis disclosed in U.S. Provisional Patent Appl. No. 62/831,017, filed Apr.8, 2019, the disclosure of which is hereby incorporated by reference.

In the various embodiments in which a developer solution is used, thedeveloper solution may be a mixture of methanol (which serves as asolvent), DMSO (which serves as a stabilizing agent), and sodiumnitroprusside (SNP). Various other solvents can be used in place ofmethanol, such as glycerol, methyl lactate, ethyl lactate, or butyllactate. In the case of acetone measurement, the SNP in the developersolution reacts with imines that are formed in the porous structure 430from acetone in the breath sample bonding with the reactive material inthe porous structure. This reaction produces the measurable color changeused to measure the quantity of extracted acetone, and thus theconcentration of acetone in the breath sample.

Base Unit

FIGS. 18A-18E illustrate various views of an embodiment of a base unitthat may be used to analyze samples collected in sample capturecartridges as disclosed herein. In some embodiments, the various samplecollection whistles disclosed herein may be used remotely from the baseunit, and sample collection cartridges may be analyzed after collectingthe samples when the user brings the sample collection cartridge to thebase unit. FIG. 18A shows a top-biased front three-quarters view of anembodiment of a base unit. FIG. 18B shows a side view of an embodimentof a base unit. FIG. 18C shows a front view of an embodiment of a baseunit. FIG. 18D shows a top view of an embodiment of a base unit. FIG.18E shows a top-biased front three-quarters view of an embodiment of abase unit having a cartridge tray in an extended position. As shown inFIGS. 18A-18E, the base unit 500 may include a housing lower 510,housing middle 512, housing upper 514, and a cartridge tray 570. Thecartridge tray 570 of the base unit 500 may be configured to accept andhold a sample capture cartridge 100, as shown in FIG. 18E.

FIG. 19A-21C show select internal components of the base unit 500 ofFIGS. 18A-18E.

FIGS. 22A-22C illustrate various views of an embodiment of a dropper tipthat may be used in connection with various developer solution bottlesto control the drop size produced during dispensing of the developersolution. As explained above, in embodiments in which a porous frit orstructure is used to extract the analyte from the breath sample, thedeveloper solution may alternatively be dispensed from a sponge

FIGS. 23A-23B show various views of a sample capture cartridge 100loaded in a base unit.

FIGS. 24A-24 B illustrate various view of an embodiment of a base unitthat may be used to analyze samples collected in sample capturecartridges as disclosed herein.

FIG. 25 illustrates a system that may be used to capture and analyze(among other potential actions) a breath sample. The system includes amobile device, e.g., an iPhone, a sample collection whistle, and a baseunit.

FIGS. 31A-31E illustrate various view of an embodiment of a base unitthat may be used to analyze samples collected in sample capturecartridges as disclosed herein. FIG. 31A shows the base unit from atop-front biased three-quarters view. FIG. 31 B shows the base unit fromthe front. FIG. 31C shows the base unit from the back. FIG. 31D showsthe base unit from the right. FIG. 31E shows the base unit from theleft. FIG. 32A-32C show select internal components of the base unit ofFIGS. 31A-31E.

In some embodiments, the base unit is configured to hold and store adeveloper solution for use in analyzing samples collected in samplecapture cartridges. The base unit may be further configured to accept aused sample capture cartridge 100 in a tray, which can be withdrawn intothe body of the base unit. The body of the base unit may besubstantially sealed from light pollution as some developer solutionsmay be light sensitive. The base unit may be further configured todispense a set volume of developer solution into the used sample capturecartridge 100 then to analyze the developed sample using a light sourceand detector pair.

In some embodiments, the base unit holds a developer tank containing thedeveloper solution. In some embodiments, the base unit dispensesdeveloper solution from the developer tank using, at least partially,gravity. As such, some embodiments of the base unit may be sensitive togravity (e.g., if the base unit is not vertical or substantiallyvertical, the developer solution may not dispense properly or at all).To address any sensitivity to gravity, some embodiments of the base unitmay include a tilt sensor, e.g., an accelerometer, configured to detectwhen the base unit is impermissibly tilted. For example, the titlesensor may be configured to disable the base unit (e.g., from performinga test analysis) when the base unit is tilted (e.g., off vertical) bymore than about 1 degree, more than about 2 degrees, more than about 3degrees, more than about 4 degrees, more than about 5 degrees, more thanabout 6 degrees, more than about 7 degrees, more than about 8 degrees,more than about 9 degrees, more than about 10 degrees, more than about15 degrees, or more than about 20 degrees.

In some embodiments, the base unit includes a developer tank coverconfigured to cover the dispensing portion of the tank when not in use,such that the tank does not drip any developer solution on components ofthe base unit below it. The developer tank cover may be a sliding tray,spring-loaded from the rear, such that when no sample capture cartridge100 is in the developer solution, the developer tank cover slidesforward to cover the tip of the developer tank (the developer tank maybe, for example, lowered into a cup on the developer tank cover when notin use). The developer tank cover may be configured such that when asample capture cartridge 100 is placed in the base unit, e.g., a slidingtray in the base unit, for analysis, the sample capture cartridge 100pushes the developer tank cover out of the way so that the developertank may descend and dispense developer solution into the sample capturecartridge 100.

In some embodiments, the base unit is comparatively or relatively small,e.g., a hand-held, or a table-top, base unit. The base unit may begenerally defined by a height (e.g., a dimension from the bottom of thebase unit to the top of the base unit), a depth (e.g., a dimension fromthe front of the base unit to the back of the base unit), and a width(e.g., a dimension from a first side of the base unit to the other,opposite side of the base unit). In some embodiments, that height of thebase unit is about 4.5 inches. In some embodiments, the height of thebase unit is between about 1-12 inches, between about 1.5-11.5 inches,between about 2-11 inches, between about 2.5-10.5 inches, between about3-10 inches, between about 3.5-9.5 inches, between about 4-9 inches,between about 4.5-8.5 inches, between about 5-8 inches, between about5.5-7.5 inches, or between about 6-7 inches. In some embodiments, theheight of the base unit is between about 3-30 inches, between about 4-25inches, between about 5-20 inches, between about 6-15 inches, or betweenabout 7-10 inches. In some embodiments, the depth of the base unit isabout 4 inches. In some embodiments, the depth of the base unit isbetween about 1-10 inches, between about 1.5-9.5 inches, between about2-9 inches, between about 2.5-8.5 inches, between about 3-8 inches,between about 3.5-7.5 inches, between about 4-7 inches, between about4.5-6.5 inches, or between about 5-6 inches. In some embodiments, thedepth of the base unit is between about 2-20 inches, between about2.5-18 inches, between about 3-16 inches, between about 3.5-14 inches,between about 4-14 inches, between about 4.5-12 inches, between about5-10 inches, between about 5.5-8 inches, or between about 6-7 inches. Insome embodiments, the width of the base unit is about 2 inches. In someembodiments, the width of the base unit is between about 0.5-5 inches,between about 0.75-4.5 inches, between about 1-4 inches, between about1.25-3.5 inches, between about 1.5-3.25 inches, between about 1.75-3inches, or between about 2-2.75 inches. In some embodiments, the widthof the base unit is between about 1-20 inches, between about 1.5-18inches, between about 2-16 inches, between about 2.5-14 inches, betweenabout 3-12 inches, between about 3.5-10 inches, between about 4-8inches, or between about 4.5-6 inches.

Developer Tank

The developer tank held by the base unit may be a user-replaceable tankfor holding a developer solution. In some embodiments, the solution thatthis tank is designed to house and dispense is a challenging liquid tomanage. For example, in some embodiments, the developer solution isviscous. In some embodiments, the developer solution is light sensitive.In some embodiments, the developer solution produces a residue upondrying. In some embodiments, the developer solution has a lower boilingpoint. In some embodiments, the developer solution is flammable. In someembodiments, the developer solution may suffer from all of theselimitations: it may be comparatively viscous, be flammable, haveUV-light sensitivity, produce a crust-like residue (post dry-out),and/or have a low boiling point (which may cause pressurization ornegative pressure within any rigid storage vessel). Developer tanks asdisclosed herein address each of these specialized needs.

In some embodiments, the developer solution comprises dimethyl sulfoxide(DMSO), methanol, and sodium nitroprusside (SNP). Dimethyl sulfoxide isa viscous. Methanol is flammable. Sodium nitroprusside is lightsensitive. In some embodiments, the developer solution comprises about24 mL of dimethyl sulfoxide, about 120 mL of methanol, and about 4.8 gof sodium nitroprusside. However, other ratios may be used.Additionally, developer solutions containing or comprising entirelydifferent ingredients or components may be used and/or dispensed fromdevelop tanks as disclosed herein.

In some embodiments, the developer solution tank 3300 disclosed hereinis configured to be used in a small, e.g., hand-held, or table-top, baseunit. For example, in some embodiments, the developer solution tank 3300has a volume (e.g., a volume of developer solution in a full developersolution tank 3300) of about 1.2 mL. In some embodiments, the developersolution tank 3300 has a maximum developer solution volume that is lessthan about 20 cc, less than about 18 cc, less than about 16 cc, lessthan about 14 cc, less than about 12 cc, less than about 10 cc, lessthan about 9 cc, less than about 8 cc, less than about 7 cc, less thanabout 6 cc, less than about 5 cc, less than about 4.5 cc, less thanabout 4 cc, less than about 3.5 cc, less than about 3 cc, less thanabout 2.5 cc, less than about 2 cc, less than about 1.75 cc, less thanabout 1.5 cc, less than about 1.25 cc, less than about 1 cc, less thanabout 0.9 cc, less than about 0.8 cc, less than about 0.7 cc, less thanabout 0.6 cc, or less than about 0.5 cc. In some embodiments, thedeveloper solution tank 3300 has an end-to-end length of less than about5 inches, less than about 4.5 inches, less than about 4 inches, lessthan about 3.5 inches, less than about 3 inches, less than about 2.5inches, less than about 2 inches, less than about 1.5 inches, less thanabout 1 inch, or less than about 0.5 inches. In some embodiments thedeveloper solution tank 3300 has a side-top-side width of less thanabout 4.5 inches, less than about 4 inches, less than about 3.5 inches,less than about 3 inches, less than about 2.5 inches, less than about 2inches, less than about 1.5 inches, less than about 1 inch, or less thanabout 0.5 inches.

FIGS. 33A-33C show various views of an embodiment of a developersolution tank 3300. FIG. 33A shows a side view of the developer solutiontank 3300. FIG. 33B shows a bottom-biased three-quarters view of thedeveloper solution tank 3300. FIG. 33C shows a cross-sectional view ofthe developer solution tank 3300. The developer solution tank 3300 has atank body top portion 3311, a tank body 3310, a tank body lower portion3312, and a nozzle 3320. The tank body 3310, tank body lower portion3312, and nozzle 3320 may be formed as a unitary part and the tank bodytop portion 3311 formed as a separate part and added to the developersolution tank 3300 after filling the developer solution tank 3300 withthe developer solution. The connection between the tank body top portion3311 may have a seal, e.g., an o-ring or other type of seal. In someembodiments, the tank body top portion 3311 is welded, e.g.,ultrasonically welded to the tank body 3310.

With reference to FIG. 33B, the nozzle 3320 comprises various portionsthat move respect to the housing of the developer solution tank 3300,e.g., the nozzle housing 3322. The portions of the nozzle 3320 that movewith respect to the nozzle housing 3322 include the dispenser tip 3332,which is connected to the connecting rod 3340, the dispenser tip o-ring3331 surrounding the dispenser tip 3332, and the dispenser o-ring flange3333 configured to hold the dispenser tip o-ring 3331 in place aroundthe dispenser tip 3332.

In some embodiments, the nozzle recess 3321 is configured to catch smallvolumes of developer solution that are successfully deposited into asample capture cartridge 100 during sample analysis. In addition, thenozzle recess 3321 may serve to hold and/or accumulate dried crusts fromsuch excess developer solution that is not successfully deposited into asample capture cartridge 100 during sample analysis.

With continued reference to FIG. 33B, the bleed valve 3350 comprises ableed valve housing 3352 surrounding the connecting rod 3340 which has ableed valve o-ring 3351 in a bleed valve o-ring recess 3353 near orproximal its upper end.

The connecting rod 3340 extend from the dispenser tip 3332 and thedispenser o-ring flange 3333 (which extend out of the dispenser valve3330) all the way through and out of the bleed valve housing 3352 of thebleed valve 3350. The spring 3342 surrounds the connecting rod 3340 andis biased on its upper end against the bleed valve housing 3352, whichis held stationary with respect to the rest of the developer solutiontank 3300, and is biased on its lower end against the dispenser o-ringflange 3333, which is movable with respect to the housing of thedeveloper solution tank 3300.

In some embodiments, the developer solution tank 3300 is configured tostabilize its own internal pressure prior to dispensing the liquidsolution contained therein. In some embodiments, the developer solutiontank 3300 is configured to dispense onto a surface that can aid in thedispensing process by wicking liquid from the dispenser valve 3330 ofthe nozzle 3320, e.g., a porous surface. In some embodiments thedeveloper solution tank 3300 is configured to dispense onto a surfacethat does not wick liquid from the dispenser valve 3330 of the nozzle3320.

In some embodiments, the developer solution tank 3300 is configured tosequentially dispense reproducible volumes of developer solution (e.g.,similar volumes for sequential tests). In some embodiments, thedeveloper solution tank 3300 is configured to dispense developersolution at a substantially constant flow rate (e.g., the volume of thedeveloper solution dispensed may be determined based on the time thedeveloper solution tank 3300 is dispensing. In some embodiments, thedeveloper solution tank 3300 is configured to dispense about 60-70 μLper dispensing (e.g., this may be based on flow rate and time dispensingat a given, or variable, flow rate). In some embodiments, the developersolution tank is configured to dispense between about 10-300 μL, betweenabout 15-280 μL, between about 20-260 μL, between about 25-240 μL,between about 30-220 μL, between about 35-200 μL, between about 40-180μL, between about 45-160 μL, between about 50-140 μL, between about55-120 μL, between about 60-100 μL, between about 65-80 μL, or betweenabout 70-75 μL. In some embodiments, the developer solution tank 3300has a substantially continuous and/or stable flow rate such that given asubstantial time open or dispensing, the variance between subsequentdispensings is less than about 30 μL, less than about 29 μL, less thanabout 28 μL, less than about 27 μL, less than about 26 μL, less thanabout 25 μL, less than about 24 μL, less than about 23 μL, less thanabout 22 μL, less than about 21 μL, less than about 20 μL, less thanabout 19 μL, less than about 18 μL, less than about 17 μL, less thanabout 16 μL, less than about 15 μL, less than about 14 μL, less thanabout 13 μL, less than about 12 μL, less than about 11 μL, less thanabout 10 μL, less than about 9 μL, less than about 8 μL, less than about7 μL, less than about 6 μL, less than about 5 pt, less than about 4 μL,less than about 3 μL, less than about 2 μL, or less than about 1 μL. Insome embodiments, the developer solution tank 3300 increases in accuracyover time. The volumetric variance of each drop after the first fewdrops may be less than the volumetric variance of each drop for thefirst few drops. For example, the volumetric variance of each drop forthe first few drops dispensed from the developer solution tank 3300 isabout ±10 μL and the volumetric variance of each subsequent drop isabout ±5 μL. In some embodiments, the volumetric variance of each dropfor the first few drops (e.g., less than about 10, 9, 8, 7, 6, 5, 4, 3,2, 1) is about ±20 μL, ±18 μL, ±16 μL, ±14 μL, ±12 μL, ±10 μL, ±8 μL, ±6μL, ±4 μL, ±2 μL, and the volumetric variance of each subsequent drop isabout ±18 μL, ±16 μL, ±14 μL, ±12 μL, ±10 μL, ±8 μL, ±6 μL, ±4 μL, ±2μL, ±1 μL.

FIGS. 34A-34B illustrate enlarged views of the nozzle 3320 of thedeveloper solution tank 3300. FIG. 34A shows the dispenser valve 3330 ofthe nozzle 3320 in a closed configuration. FIG. 34B shows the dispenservalve 3330 of the nozzle 3320 in an open configuration. At the lower endof the tank, e.g., at nozzle 3320, the small, cylindrical tip of thedispenser tip 3332 protrudes out of a hole in the dispenser valve 3330of the nozzle 3320. In some embodiments, when closed the dispenser tip3332 protrudes approximately 2.38 mm past the end of the nozzle 3320. Insome embodiments, when closed the dispenser tip 3332 protrudes past theend of the nozzle 3320 by less than about 3 mm, less than about 4 mm,less than about 3.8 mm, less than about 3.6 mm, less than about 3.4 mm,less than about 3.2 mm, less than about 3 mm, less than about 2.8 mm,less than about 2.6 mm, less than about 2.4 mm, less than about 2.2 mm,less than about 2 mm, less than about 1.8 mm, less than about 1.6 mm,less than about 1.4 mm, less than about 1.2 mm, less than about 1 mm, orless than about 0.8 mm,

When the dispenser valve 3330 of the nozzle 3320 is brought to asurface, such as porous polyethylene (such as may be used in connectionwith one or more embodiments of the porous bowl 130 disclosed herein),the dispenser tip 3332 is depressed. In some embodiments, the dispensertip 3332 is depressed until the body of the nozzle 3320 touches thesurface and the dispenser tip 3332 is telescopically pushed inside,e.g., completely inside, the body of the nozzle 3320, such as is shownin FIG. 34B.

As shown in FIG. 34C, the dispenser tip 3332 is backed by spring 3342,e.g., an internal compression return spring, that forces the dispensertip 3332 back out of the nozzle 3320 when dispensing stops and thedispenser valve 3330 is withdrawn from the surface, e.g., the poroussurface. When the dispenser tip 3332 is depressed, dispenser tip o-ring3331 is unseated from within the nozzle housing 3322 and a flow path isopened to allow the liquid solution stored above to flow. In someembodiments, gravity facilitates or helps to promote flow of developsolution out of the dispenser valve 3330 of the nozzle 3320. In someembodiments, along with gravity, wicking by a porous surface, such asthe porous surface of one or more porous bowls 130 disclosed herein,facilitates or helps to promote flow of develop solution out of thedispenser valve 3330 of the nozzle 3320. When dispensing stops, the tiptravels back out of the dispenser valve 3330 of the nozzle 3320 anddispenser tip o-ring 3331 is reseated against the nozzle housing 3322(e.g., when the spring 3342 pushes downward on the dispenser o-ringflange 3333, thereby blocking off the flow path, e.g., completelyblocking off the flow path.

In some embodiments, the developer solution tank 3300 is a rigid tank.In a rigid tank, any volume of developer solution that is lost duringdispensing must be replaced with air from the outside of the developersolution tank 3300. Bleed valve 3350, located at the top of thedeveloper solution tank 3300, opposite the dispenser valve 3330 andnozzle 3320, is configured to allow this air to enter.

In some embodiments, the bleed valve 3350 opens and closes at specifictimes. In some embodiments, the bleed valve 3350 advantageously opensshortly before, e.g., a fraction of a second before, the dispenser valve3330 of the nozzle 3320 opens. In some embodiments, a base unitconfigured to hold and/or move the developer solution tank 3300 includesa programmed controller that controls the movement of the developersolution tank 3300 as well as the opening and/or closing of the bleedvalve 3350 and/or the dispenser valve 3330 or other automated tasks(such base unit may also include a wireless transceiver forcommunicating with a smartphone). In some embodiments, the bleed valve3350 opens at the same time as, e.g., simultaneously with, the dispenservalve 3330 of the nozzle 3320 opens. In some embodiments, the bleedvalve 3350 opens shortly after, e.g., a fraction of a second after, thedispenser valve 3330 of the nozzle 3320 opens. The relationship of thetiming of the closure of the bleed valve 3350 of the timing of theclosure of the dispenser valve 3330 may be controlled with the distancebetween the dispenser o-ring flange 3333 and the bleed valve o-ringrecess 3353 on the connecting rod 3340 as well as the depth of thenozzle housing 3322 and the depth of the bleed valve housing 3352 (e.g.,the distance that the o-ring of the respective structure may travel intothe respective housing). As will be readily appreciated, the bleed valve3350 may advantageously close when dispensing is complete to preventevaporation of a volatile liquid contained within the developer solutiontank 3300.

FIG. 35A illustrates the bleed valve 3350 in a closed configuration. Asshown, the bleed valve o-ring 3351 (nested within bleed valve o-ringrecess 3353) is seated within the bleed valve housing 3352 (note thatthe bleed valve o-ring recess 3353 may be forcibly seated against thebleed valve housing 3352 as spring 3342 pushes down on the dispensero-ring flange 3333 fixed to the connecting rod 3340). The closedconfiguration of the bleed valve 3350 shown in FIG. 35A advantageouslyprevents evaporation of the developer solution between dispensings: thisis particularly important when a low boiling point developer solution isbeing used.

FIG. 35B illustrates the bleed valve 3350 in an open configuration. Asshown, the bleed valve o-ring 3351 is lifted off the bleed valve housing3352 opening a passageway into the body of the developer solution tank3300, and thereby advantageously allowing the equalization of pressurewithin the tank body 3310 as the developer solution within the developersolution tank 3300 is dispensed.

Because the bleed valve 3350 and the dispenser valve 3330 are connectedmechanically, e.g., via the connecting rod 3340, the developer solutiontank 3300 may advantageously be provided with a dispensing lock toprevent accidental dispensing, e.g., during shipping or installation. Insome embodiments, the dispensing lock may simply be a clip that attachesover the bleed valve 3350, e.g., lockingly engaging over the uppermostend of the connecting rod 3340. In this way, when the uppermost end ofthe connecting rod 3340 is locked in place, the dispenser tip 3332 ofthe dispenser valve 3330 may not move within the nozzle 3320 and thedispenser tip o-ring 3331 may not unseat from within the nozzle housing3322. Thus, when the dispensing lock is in place, the developer solutiontank 3300 is not capable of dispensing. The dispensing lock may beremoved before the developer solution tank 3300 is used to develop atest sample, e.g., before installing the developer solution tank 3300 ina base unit.

The foregoing description and examples has been set forth merely toillustrate the disclosure and are not intended as being limiting. Eachof the disclosed aspects and embodiments of the present disclosure maybe considered individually or in combination with other aspects,embodiments, and variations of the disclosure. In addition, unlessotherwise specified, none of the steps of the methods of the presentdisclosure are confined to any particular order of performance.Modifications of the disclosed embodiments incorporating the spirit andsubstance of the disclosure may occur to persons skilled in the art andsuch modifications are within the scope of the present disclosure.Furthermore, all references cited herein are incorporated by referencein their entirety.

Terms of orientation used herein, such as “top,” “bottom,” “horizontal,”“vertical,” “longitudinal,” “lateral,” and “end” are used in the contextof the illustrated embodiment. However, the present disclosure shouldnot be limited to the illustrated orientation. Indeed, otherorientations are possible and are within the scope of this disclosure.Terms relating to circular shapes as used herein, such as diameter orradius, should be understood not to require perfect circular structures,but rather should be applied to any suitable structure with across-sectional region that can be measured from side-to-side. Termsrelating to shapes generally, such as “circular” or “cylindrical” or“semi-circular” or “semi-cylindrical” or any related or similar terms,are not required to conform strictly to the mathematical definitions ofcircles or cylinders or other structures, but can encompass structuresthat are reasonably close approximations.

Conditional language used herein, such as, among others, “can,” “might,”“may,” “e.g.,” and the like, unless specifically stated otherwise, orotherwise understood within the context as used, is generally intendedto convey that some embodiments include, while other embodiments do notinclude, certain features, elements, and/or states. Thus, suchconditional language is not generally intended to imply that features,elements, blocks, and/or states are in any way required for one or moreembodiments or that one or more embodiments necessarily include logicfor deciding, with or without author input or prompting, whether thesefeatures, elements and/or states are included or are to be performed inany particular embodiment.

Conjunctive language, such as the phrase “at least one of X, Y, and Z,”unless specifically stated otherwise, is otherwise understood with thecontext as used in general to convey that an item, term, etc. may beeither X, Y, or Z. Thus, such conjunctive language is not generallyintended to imply that certain embodiments require the presence of atleast one of X, at least one of Y, and at least one of Z.

The terms “approximately,” “about,” and “substantially” as used hereinrepresent an amount close to the stated amount that still performs adesired function or achieves a desired result. For example, in someembodiments, as the context may dictate, the terms “approximately”,“about”, and “substantially” may refer to an amount that is within lessthan or equal to 10% of the stated amount. The term “generally” as usedherein represents a value, amount, or characteristic that predominantlyincludes or tends toward a particular value, amount, or characteristic.As an example, in certain embodiments, as the context may dictate, theterm “generally parallel” can refer to something that departs fromexactly parallel by less than or equal to 20 degrees.

Unless otherwise explicitly stated, articles such as “a” or “an” shouldgenerally be interpreted to include one or more described items.Accordingly, phrases such as “a device configured to” are intended toinclude one or more recited devices. Such one or more recited devicescan be collectively configured to carry out the stated recitations. Forexample, “a processor configured to carry out recitations A, B, and C”can include a first processor configured to carry out recitation Aworking in conjunction with a second processor configured to carry outrecitations B and C.

The terms “comprising,” “including,” “having,” and the like aresynonymous and are used inclusively, in an open-ended fashion, and donot exclude additional elements, features, acts, operations, and soforth. Likewise, the terms “some,” “certain,” and the like aresynonymous and are used in an open-ended fashion. Also, the term “or” isused in its inclusive sense (and not in its exclusive sense) so thatwhen used, for example, to connect a list of elements, the term “or”means one, some, or all of the elements in the list.

Overall, the language of the claims is to be interpreted broadly basedon the language employed in the claims. The language of the claims isnot to be limited to the non-exclusive embodiments and examples that areillustrated and described in this disclosure, or that are discussedduring the prosecution of the application.

Although systems and methods for breath collection, sampling,segmentation, and analysis have been disclosed in the context of certainembodiments and examples, this disclosure extends beyond thespecifically disclosed embodiments to other alternative embodimentsand/or uses of the embodiments and certain modifications and equivalentsthereof. Various features and aspects of the disclosed embodiments canbe combined with or substituted for one another in order to form varyingmodes of systems and methods for breath collection, sampling,segmentation, and analysis. The scope of this disclosure should not belimited by the particular disclosed embodiments described herein.

Certain features that are described in this disclosure in the context ofseparate implementations can be implemented in combination in a singleimplementation. Conversely, various features that are described in thecontext of a single implementation can be implemented in multipleimplementations separately or in any suitable subcombination. Althoughfeatures may be described herein as acting in certain combinations, oneor more features from a claimed combination can, in some cases, beexcised from the combination, and the combination may be claimed as anysubcombination or variation of any subcombination.

While the methods and devices described herein may be susceptible tovarious modifications and alternative forms, specific examples thereofhave been shown in the drawings and are herein described in detail. Itshould be understood, however, that the invention is not to be limitedto the particular forms or methods disclosed, but, to the contrary, theinvention is to cover all modifications, equivalents, and alternativesfalling within the spirit and scope of the various embodiments describedand the appended claims. Further, the disclosure herein of anyparticular feature, aspect, method, property, characteristic, quality,attribute, element, or the like in connection with an embodiment can beused in all other embodiments set forth herein. Any methods disclosedherein need not be performed in the order recited. Depending on theembodiment, one or more acts, events, or functions of any of thealgorithms, methods, or processes described herein can be performed in adifferent sequence, can be added, merged, or left out altogether (e.g.,not all described acts or events are necessary for the practice of thealgorithm). In some embodiments, acts or events can be performedconcurrently, e.g., through multi-threaded processing, interruptprocessing, or multiple processors or processor cores or on otherparallel architectures, rather than sequentially. Further, no element,feature, block, or step, or group of elements, features, blocks, orsteps, are necessary or indispensable to each embodiment. Additionally,all possible combinations, subcombinations, and rearrangements ofsystems, methods, features, elements, modules, blocks, and so forth arewithin the scope of this disclosure. The use of sequential, ortime-ordered language, such as “then,” “next,” “after,” “subsequently,”and the like, unless specifically stated otherwise, or otherwiseunderstood within the context as used, is generally intended tofacilitate the flow of the text and is not intended to limit thesequence of operations performed. Thus, some embodiments may beperformed using the sequence of operations described herein, while otherembodiments may be performed following a different sequence ofoperations.

Moreover, while operations may be depicted in the drawings or describedin the specification in a particular order, such operations need not beperformed in the particular order shown or in sequential order, and alloperations need not be performed, to achieve the desirable results.Other operations that are not depicted or described can be incorporatedin the example methods and processes. For example, one or moreadditional operations can be performed before, after, simultaneously, orbetween any of the described operations. Further, the operations may berearranged or reordered in other implementations. Also, the separationof various system components in the implementations described hereinshould not be understood as requiring such separation in allimplementations, and it should be understood that the describedcomponents and systems can generally be integrated together in a singleproduct or packaged into multiple products. Additionally, otherimplementations are within the scope of this disclosure.

Some embodiments have been described in connection with the accompanyingfigures. Certain figures are drawn and/or shown to scale, but such scaleshould not be limiting, since dimensions and proportions other than whatare shown are contemplated and are within the scope of the embodimentsdisclosed herein. Distances, angles, etc. are merely illustrative and donot necessarily bear an exact relationship to actual dimensions andlayout of the devices illustrated. Components can be added, removed,and/or rearranged. Further, the disclosure herein of any particularfeature, aspect, method, property, characteristic, quality, attribute,element, or the like in connection with various embodiments can be usedin all other embodiments set forth herein. Additionally, any methodsdescribed herein may be practiced using any device suitable forperforming the recited steps.

The methods disclosed herein may include certain actions taken by apractitioner; however, the methods can also include any third-partyinstruction of those actions, either expressly or by implication. Forexample, actions such as “positioning an electrode” include “instructingpositioning of an electrode.”

In summary, various embodiments and examples of systems and methods forbreath collection, sampling, segmentation, and analysis have beendisclosed. Although the systems and methods for breath collection,sampling, segmentation, and analysis have been disclosed in the contextof those embodiments and examples, this disclosure extends beyond thespecifically disclosed embodiments to other alternative embodimentsand/or other uses of the embodiments, as well as to certainmodifications and equivalents thereof. This disclosure expresslycontemplates that various features and aspects of the disclosedembodiments can be combined with, or substituted for, one another. Thus,the scope of this disclosure should not be limited by the particulardisclosed embodiments described herein, but should be determined only bya fair reading of the claims that follow.

The ranges disclosed herein also encompass any and all overlap,sub-ranges, and combinations thereof. Language such as “up to,” “atleast,” “greater than,” “less than,” “between,” and the like includesthe number recited. Numbers preceded by a term such as “about” or“approximately” include the recited numbers and should be interpretedbased on the circumstances (e.g., as accurate as reasonably possibleunder the circumstances, for example ±5%, ±10%, ±15%, etc.). Forexample, “about 1 V” includes “1 V.” Phrases preceded by a term such as“substantially” include the recited phrase and should be interpretedbased on the circumstances (e.g., as much as reasonably possible underthe circumstances). For example, “substantially perpendicular” includes“perpendicular.” Unless stated otherwise, all measurements are atstandard conditions including temperature and pressure.

The invention claimed is:
 1. A method for analyzing breath, comprising:routing a breath sample of a human subject through a porous structurethat comprises a blend of a reactive material and a resin materialformed into a selected shape, causing the porous structure to extract ananalyte of interest from the breath sample; and subsequently, dispensinga developer solution into the porous structure by bringing the porousstructure into contact with a sponge that holds a volume of thedeveloper solution, wherein the developer solution induces a measurablechange reflective of a concentration of the analyte of interest in thebreath sample.
 2. The method of claim 1, wherein the sponge is a bondedfiber reservoir.
 3. The method of claim 1, wherein the sponge comprisesfibers of polyethylene and fibers of polypropylene.
 4. The method ofclaim 1, wherein the sponge has an average pore size that is greaterthan an average pore size of the porous structure.
 5. The method ofclaim 1, wherein the reactive material comprises functionalized silicaparticles.
 6. The method of claim 1, wherein the resin materialcomprises at least one of polyethylene or polypropylene.
 7. The methodof claim 1, wherein the porous structure is capable of extracting andreacting with acetone in the breath sample.
 8. The method of claim 1,wherein the porous structure has a puck shape.
 9. The method of claim 1,wherein the sponge is provided as a pad onto which a user depresses acartridge containing the porous structure.
 10. The method of claim 1,wherein the porous structure and the sponge are provided in a cartridge,and the method further comprises applying a force the brings the spongeand porous structure into contact with each other in the cartridge afterthe breath sample is routed through the porous structure.
 11. The methodof claim 1, wherein the porous structure is a solid containing the blendof the reactive material and the resin material.
 12. The method of claim11, wherein the solid is molded into the selected shape.
 13. The methodof claim 11, wherein the shape is a puck shape.
 14. An apparatus foranalyzing breath, comprising a porous structure that comprises a blendof a reactive material and a resin material, the porous structurecapable of extracting an analyte of interest from the breath sample whenthe breath sample is passed through the porous device; and a sponge thatholds a volume of developer solution, the sponge configured to deliverthe developer solution to the porous structure when the sponge andporous structure are brought into contact with each other, the developersolution capable of inducing a measurable change reflecting a quantityof the analyte of interest extracted by the porous structure.
 15. Theapparatus of claim 14, wherein the porous structure and the sponge arehoused within a disposable cartridge.
 16. The apparatus of claim 15,wherein the porous structure is a solid and has a puck shape.
 17. Theapparatus of claim 14, wherein the sponge is part of a pad onto which auser depresses a cartridge containing the porous structure.
 18. Theapparatus of claim 14, wherein the sponge is a bonded fiber reservoir.19. The apparatus of claim 14, wherein the sponge comprises fibers ofpolyethylene and fibers of polypropylene.
 20. The apparatus of claim 14,wherein the sponge has an average pore size that is greater than anaverage pore size of the porous structure.
 21. The apparatus of claim14, wherein the reactive material comprises functionalized silicaparticles, and the functionalized silica particles and resin materialare molded together into a solid.
 22. The apparatus of claim 14, whereinthe resin material comprises at least one of polyethylene orpolypropylene, and the reactive material and resin material are moldedtogether into a solid.
 23. The apparatus of claim 14, wherein the porousstructure is a solid and is capable of extracting acetone in the breathsample.
 24. The apparatus of claim 14, wherein the porous structure andthe sponge are housed within a disposable cartridge with an air gapseparating the porous structure from the sponge, and the apparatusfurther comprises a motor or solenoid that causes the sponge and porousstructure to be brought into contact with each other.
 25. A method,comprising: causing a breath sample to be passed through a porousstructure that includes a reactive material, wherein the porousstructure extracts an analyte of interest from the breath sample; andsubsequently, bringing the porous structure into contact with a spongethat holds a developer solution, to thereby cause developer solution tobe transferred from the sponge into the porous structure, wherein thedeveloper solution induces a measurable change reflective of a quantityof the analyte of interest extracted by the porous structure.
 26. Themethod of claim 25, wherein causing the breath sample to be passedthrough the porous structure comprises, while a user exhales into abreath input device, switching a valve to cause a selected portion ofexhaled breath to be routed through the porous structure.
 27. The methodof claim 25, wherein the porous structure is a solid that contains ablend of the reactive material and a resin material.
 28. The method ofclaim 27, wherein the porous structure is molded into a selected shape.29. The method of claim 27, wherein the porous structure has a puckshape.
 30. The method of claim 25, wherein the porous structure and thesponge are provided in a cartridge, and the method further comprisesapplying a force that brings the sponge and porous structure intocontact with each other in the cartridge after the breath sample ispassed through the porous structure.
 31. The method of claim 25, whereinthe sponge is provided as a pad onto which a user depresses a cartridgecontaining the porous structure.